Environmental enrichment

Last updated
A rodent is not stimulated by the environment in a wire cage, and this affects its brain negatively, particularly the complexity of its synaptic connections Rat coming out cage.jpg
A rodent is not stimulated by the environment in a wire cage, and this affects its brain negatively, particularly the complexity of its synaptic connections

Environmental enrichment is the stimulation of the brain by its physical and social surroundings. Brains in richer, more stimulating environments have higher rates of synaptogenesis and more complex dendrite arbors, leading to increased brain activity. This effect takes place primarily during neurodevelopment, but also during adulthood to a lesser degree. With extra synapses there is also increased synapse activity, leading to an increased size and number of glial energy-support cells. Environmental enrichment also enhances capillary vasculation, providing the neurons and glial cells with extra energy. The neuropil (neurons, glial cells, capillaries, combined) expands, thickening the cortex. Research on rodent brains suggests that environmental enrichment may also lead to an increased rate of neurogenesis.

Contents

Research on animals finds that environmental enrichment could aid the treatment and recovery of numerous brain-related dysfunctions, including Alzheimer's disease and those connected to aging, whereas a lack of stimulation might impair cognitive development. Moreover, this research also suggests that environmental enrichment leads to a greater level of cognitive reserve, the brain's resilience to the effects of conditions such as aging and dementia.

Research on humans suggests that lack of stimulation delays and impairs cognitive development. Research also finds that attaining and engaging in higher levels of education, environments in which people participate in more challenging cognitively stimulating activities, results in greater cognitive reserve.

Early research

Donald O. Hebb in 1947 found that rats raised as pets performed better on problem solving tests than rats raised in cages. [1] His research, however, did not investigate the brain nor use standardized impoverished and enriched environments. Research doing this first was started in 1960 at the University of California, Berkeley by Mark Rosenzweig, who compared single rats in normal cages, and those placed in ones with toys, ladders, tunnels, running wheels in groups. This found that growing up in enriched environments affected enzyme cholinesterase activity. [2] This work led in 1962 to the discovery that environmental enrichment increased cerebral cortex volume. [3] In 1964, it was found that this was due to increased cerebral cortex thickness and greater synapse and glial numbers. [4] [5]

Also starting around 1960, Harry Harlow studied the effects of maternal and social deprivation on rhesus monkey infants (a form of environmental stimulus deprivation). This established the importance of social stimulation for normal cognitive and emotional development. [6]

Synapses

Synaptogenesis

Rats raised with environmental enrichment have thicker cerebral cortices (3.3–7%) that contain 25% more synapses. [5] [7] This effect of environmental richness upon the brain occurs whether it is experienced immediately following birth, [8] after weaning, [5] [7] [9] or during maturity. [10] When synapse numbers increase in adults, they can remain high in number even when the adults are returned to impoverished environment for 30 days [10] suggesting that such increases in synapse numbers are not necessarily temporary. However, the increase in synapse numbers has been observed generally to reduce with maturation. [11] [12] Stimulation affects not only synapses upon pyramidal neurons (the main projecting neurons in the cerebral cortex) but also stellate ones (that are usually interneurons). [13] It can also affect neurons outside the brain, such as those in the retina. [14]

Dendrite complexity

Environmental enrichment affects the complexity and length of the dendrite arbors (upon which synapses form). Higher-order dendrite branch complexity is increased in enriched environments, [13] [15] as can the length, in young animals, of distal branches. [16] Environmental enrichment rescues harmful effects of stress on dendritic complexity. [17]

Activity and energy consumption

Animals in enriched environments show evidence of increased synapse activation. [18] Synapses tend to also be much larger. [19] Gamma oscillations become larger in amplitude in the hippocampus. [20] This increased energy consumption is reflected in glial and local capillary vasculation that provides synapses with extra energy.

These energy related changes to the neuropil are responsible for increasing the volume of the cerebral cortex (the increase in synapse numbers contributes in itself hardly any extra volume).

Motor learning stimulation

Part of the effect of environmental enrichment is providing opportunities to acquire motor skills. Research on rats learning an “acrobatic” skill shows that such learning activity leads to increased synapse count. [23] [24]

Maternal transmission

Environmental enrichment during pregnancy has effects upon the fetus, such as accelerating his or her retinal development. [25]

Neurogenesis

Environmental enrichment can also lead to the formation of neurons (at least in rats) [26] and reverse both the loss of neurons in the hippocampus and memory impairment from chronic stress. [27] However, its relevance has been questioned for the behavioral effects of enriched environments. [28]

Mechanisms

Enriched environments affect the expression of genes that determine neuronal structure in the cerebral cortex and hippocampus. [29] At the molecular level, this occurs through increased concentrations of the neurotrophins NGF, NT-3, [30] [31] and changes in BDNF. [14] [32] This alters the activation of cholinergic neurons, [31] 5-HT, [33] and beta-adrenolin. [34] Another effect is to increase proteins such as synaptophysin and PSD-95 in synapses. [35] Changes in Wnt signaling have also been found to mimic in adult mice the effects of environmental enrichment upon synapses in the hippocampus. [36] Increase in neurons numbers could be linked to changes in VEGF. [37]

Rehabilitation and resilience

Research in animals suggests that environmental enrichment aids recovery from certain neurological disorders and cognitive impairments. There are two mains areas of focus: neurological rehabilitation and cognitive reserve, the brain's resistance to the effects of exposure to physical, natural, and social threats. Although most of these experiments used animal subjects, mainly rodents, researchers have pointed to the affected areas of animal brains to which human brains are most similar and used their findings as evidence to show that humans would have comparable reactions to enriched environments. The tests done on animals are thus meant to represent human simulations for the following list of conditions.

Neurological rehabilitation

Autism

A study conducted in 2011 led to the conclusion that environmental enrichment vastly improves the cognitive ability of children with autism. The study found that autistic children who receive olfactory and tactile stimulation along with exercises that stimulated other paired sensory modalities clinically improved by 42 percent while autistic children not receiving this treatment clinically improved by just 7 percent. [38] The same study also showed that there was significant clinical improvement in autistic children exposed to enriched sensorimotor environments, and a vast majority of parents reported that their child's quality of life was much better with the treatment. [38] A second study confirmed its effectiveness. The second study also found after 6 months of sensory enrichment therapy, 21% of the children who initially had been given an autism classification, using the Autism Diagnostic Observation Schedule, improved to the point that, although they remained on the autism spectrum, they no longer met the criteria for classic autism. None of the standard care controls reached an equivalent level of improvement. [39] The therapy using the methodologies is titled Sensory Enrichment Therapy. [40] [41]

Alzheimer's disease

Through environmental enrichment, researchers were able to enhance and partially repair memory deficits in mice between ages of 2 to 7 months with characteristics of Alzheimer's disease. Mice in enriched environments performed significantly better on object recognition tests and the Morris Water Maze than they had when they were in standard environments. It was thus concluded that environmental enrichment enhances visual and learning memory for those with Alzheimer's. [42] Furthermore, it has been found that mouse models of Alzheimer's disease that were exposed to enriched environment before amyloid onset (at 3 months of age) and then returned to their home cage for over 7 months, showed preserved spatial memory and reduced amyloid deposition at 13 months old, when they are supposed to show dramatic memory deficits and amyloid plaque load. These findings reveal the preventive, and long-lasting effects of early life stimulating experience on Alzheimer-like pathology in mice and likely reflect the capacity of enriched environment to efficiently stimulate the cognitive reserve. [43] A human study suggests that enriched gardens contribute to better cognitive function and independence in activities of daily living, compared to conventional sensory gardens. [44]

Huntington's disease

Research has indicated that environmental enrichment can help relieve motor and psychiatric deficits caused by Huntington's disease. It also improves lost protein levels for those with the disease, and prevents striatal and hippocampal deficits in the BDNF, located in the hippocampus. [45] These findings have led researchers to suggest that environmental enrichment has a potential to be a possible form of therapy for those with Huntington's. [45]

Parkinson's disease

Multiple studies have reported that environmental enrichment for adult mice helps relieve neuronal death, which is particularly beneficial to those with Parkinson's disease. [46] A more recent study shows that environmental enrichment particularly affects the nigrostriatal pathway, which is important for managing dopamine and acetylcholine levels, critical for motor deficits. [47] Moreover, it was found that environmental enrichment has beneficial effects for the social implications of Parkinson's disease. [47]

Stroke

Research done in animals has shown that subjects recovering in an enriched environment 15 days after having a stroke had significantly improved neurobehavioral function. In addition these same subjects showed greater capability of learning and larger infarct post-intervention than those who were not in an enriched environment. It was thus concluded that environmental enrichment had a considerable beneficial effect on the learning and sensorimotor functions on animals post-stroke. [48] A 2013 study also found that environmental enrichment socially benefits patients recovering from stroke. Researchers in that study concluded that stroke patients in enriched environments in assisted-care facilities are much more likely to be engaging with other patients during normal social hours instead of being alone or sleeping. [49]

Rett syndrome

A 2008 study found that environmental enrichment was significant in aiding recovery of motor coordination and some recovery of BDNF levels in female mice with conditions similar to those of Rett syndrome. Over the course of 30 weeks female mice in enriched environments showed superior ability in motor coordination to those in standard conditions. [50] Although they were unable to have full motor capability, they were able to prevent a more severe motor deficit by living in an enriched environment. These results combined with increased levels of BDNF in the cerebellum led researchers to conclude that an enriched environment that stimulates areas of the motor cortex and areas of the cerebellum having to do with motor learning is beneficial in aiding mice with Rett syndrome. [50]

Amblyopia

A recent study found that adult rats with amblyopia improved visual acuity two weeks after being placed into an enriched environment. [51] The same study showed that another two weeks after ending environmental enrichment, the rats retained their visual acuity improvement. Conversely, rats in a standard environment showed no improvement in visual acuity. It was thus concluded that environmental enrichment reduces GABA inhibition and increases BDNF expression in the visual cortex. As a result, the growth and development of neurons and synapses in the visual cortex were much improved due to the enriched environment. [51]

Sensory deprivation

Studies have shown that with the help of environmental enrichment the effects of sensory deprivation can be corrected. For example, a visual impairment known as "dark-rearing" in the visual cortex can be prevented and rehabilitated. In general, an enriched environment will improve, if not repair, the sensory systems animals possess. [52]

Lead poisoning

During development, gestation is one of the most critical periods for exposure to any lead. Exposure to high levels of lead at this time can lead to inferior spatial learning performance. Studies have shown that environmental enrichment can overturn damage to the hippocampus induced by lead exposure. [53] Learning and spatial memory that are dependent on the long-term potentiation of the hippocampus are vastly improve as subjects in an enriched environments had lower levels of lead concentration in their hippocampi. The findings also showed that enriched environments result in some natural protection of lead-induced brain deficits. [53]

Chronic spinal cord injuries

Research has indicated that animals suffering from spinal cord injuries showed significant improvement in motor capabilities even with a long delay in treatment after the injury when exposed to environmental enrichment. [54] Social interactions, exercise, and novelty all play major roles in aiding the recovery of an injured subject. This has led to some suggestions that the spinal cord has a continued plasticity and all efforts must be made for enriched environments to stimulate this plasticity in order to aid recovery. [54]

Maternal deprivation stress

Maternal deprivation can be caused by the abandonment by a nurturing parent at a young age. In rodents or nonhuman primates, this leads to a higher vulnerability for stress-related illness. [55] Research suggests that environmental enrichment can reverse the effects of maternal separation on stress reactivity, possibly by affecting the hippocampus, the amygdala and the prefrontal cortex. [55] [17]

Child neglect

In all children, maternal care is one of the significant influences for hippocampal development, providing the foundation for stable and individualized learning and memory. However, this is not the case for those who have experienced child neglect. Researchers determined that through environmental enrichment, a neglected child can partially receive the same hippocampal development and stability, albeit not at the same level as that of the presence of a parent or guardian. [56] The results were comparable to those of child intervention programs, rendering environmental enrichment a useful method for dealing with child neglect. [56] [ failed verification ]

Cognitive reserve

Aging

Decreased hippocampal neurogenesis is a characteristic of aging. Environmental enrichment increases neurogenesis in aged rodents by potentiating neuronal differentiation and new cell survival. [57] As a result, subjects exposed to environmental enrichment aged better due to superior ability in retaining their levels of spatial and learning memory. [57]

Prenatal and perinatal cocaine exposure

Research has shown that mice exposed to environmental enrichment are less affected by the consequences of cocaine exposure in comparison with those in standard environments. Although the levels of dopamine in the brains of both sets of mice were relatively similar, when both subjects were exposed to the cocaine injection, mice in enriched environment were significantly less responsive than those in standard environments. [58] It was thus concluded that both the activating and rewarding effects are suppressed by environmental enrichment and early exposure to environmental enrichment can help prevent drug addiction. [58]

Humans

Though environmental enrichment research has been mostly done upon rodents, similar effects occur in primates, [59] and are likely to affect the human brain. However, direct research upon human synapses and their numbers is limited since this requires histological study of the brain. A link, however, has been found between educational level and greater dendritic branch complexity following autopsy removal of the brain. [60]

Localized cerebral cortex changes

MRI detects localized cerebral cortex expansion after people learn complex tasks such as mirror reading (in this case in the right occipital cortex), [61] three-ball juggling (bilateral mid-temporal area and left posterior intraparietal sulcus), [62] and when medical students intensively revise for exams (bilaterally in the posterior and lateral parietal cortex). [63] Such changes in gray matter volume can be expected to link to changes in synapse numbers due to the increased numbers of glial cells and the expanded capillary vascularization needed to support their increased energy consumption.

Institutional deprivation

Children that receive impoverished stimulation due to being confined to cots without social interaction or reliable caretakers in low quality orphanages show severe delays in cognitive and social development. [64] 12% of them if adopted after 6 months of age show autistic or mildly autistic traits later at four years of age. [65] Some children in such impoverished orphanages at two and half years of age still fail to produce intelligible words, though a year of foster care enabled such children to catch up in their language in most respects. [66] Catch-up in other cognitive functioning also occurs after adoption, though problems continue in many children if this happens after the age of 6 months. [67]

Such children show marked differences in their brains, consistent with research upon experiment animals, compared to children from normally stimulating environments. They have reduced brain activity in the orbital prefrontal cortex, amygdala, hippocampus, temporal cortex, and brain stem. [68] They also showed less developed white matter connections between different areas in their cerebral cortices, particularly the uncinate fasciculus. [69]

Conversely, enriching the experience of preterm infants with massage quickens the maturation of their electroencephalographic activity and their visual acuity. Moreover, as with enrichment in experimental animals, this associates with an increase in IGF-1. [70]

Cognitive reserve and resilience

Another source of evidence for the effect of environment stimulation upon the human brain is cognitive reserve (a measure of the brain's resilience to cognitive impairment) and the level of a person's education. Not only is higher education linked to a more cognitively demanding educational experience, but it also correlates with a person's general engagement in cognitively demanding activities. [71] The more education a person has received, the less the effects of aging, [72] [73] dementia, [74] white matter hyperintensities, [75] MRI-defined brain infarcts, [76] Alzheimer's disease, [77] [78] and traumatic brain injury. [79] Also, aging and dementia are less in those that engage in complex cognitive tasks. [80] The cognitive decline of those with epilepsy could also be affected by the level of a person's education. [81]

See also

Notes

  1. Hebb DO (1947). "The effects of early experience on problem solving at maturity". American Psychologist. 2 (8): 306–7. doi:10.1037/h0063667.
  2. Krech D, Rosenzweig MR, Bennett EL (December 1960). "Effects of environmental complexity and training on brain chemistry". J Comp Physiol Psychol. 53 (6): 509–19. doi:10.1037/h0045402. PMID   13754181.
  3. Rosenzweig MR, Krech D, Bennett EL, Diamond MC (August 1962). "Effects of environmental complexity and training on brain chemistry and anatomy: a replication and extension". J Comp Physiol Psychol. 55 (4): 429–37. doi:10.1037/h0041137. PMID   14494091.
  4. Altman J, Das GD (December 1964). "Autoradiographic Examination of the Effects of Enriched Environment on the Rate of Glial Multiplication in the Adult Rat Brain". Nature. 204 (4964): 1161–3. Bibcode:1964Natur.204.1161A. doi:10.1038/2041161a0. PMID   14264369. S2CID   29794121.
  5. 1 2 3 4 Diamond MC, Krech D, Rosenzweig MR (August 1964). "The Effects of an Enriched Environment on the Histology of the Rat Cerebral Cortex". J. Comp. Neurol. 123: 111–20. doi:10.1002/cne.901230110. PMID   14199261. S2CID   30997263.
  6. Harlow HF, Rowland GL, Griffin GA (December 1964). "The Effect of Total Social Deprivation on the Development of Monkey Behavior". Psychiatr Res Rep Am Psychiatr Assoc. 19: 116–35. PMID   14232649.
  7. 1 2 3 Diamond MC, Law F, Rhodes H, et al. (September 1966). "Increases in cortical depth and glia numbers in rats subjected to enriched environment". J. Comp. Neurol. 128 (1): 117–26. doi:10.1002/cne.901280110. PMID   4165855. S2CID   32351844.
  8. Schapiro S, Vukovich KR (January 1970). "Early experience effects upon cortical dendrites: a proposed model for development". Science. 167 (3916): 292–4. Bibcode:1970Sci...167..292S. doi:10.1126/science.167.3916.292. PMID   4188192. S2CID   10057164.
  9. Bennett EL, Diamond MC, Krech D, Rosenzweig MR (October 1964). "Chemical and Anatomical Plasticity Brain". Science. 146 (3644): 610–9. Bibcode:1964Sci...146..610B. doi:10.1126/science.146.3644.610. PMID   14191699.
  10. 1 2 Briones TL, Klintsova AY, Greenough WT (August 2004). "Stability of synaptic plasticity in the adult rat visual cortex induced by complex environment exposure". Brain Res. 1018 (1): 130–5. doi:10.1016/j.brainres.2004.06.001. PMID   15262214. S2CID   22709746.
  11. Holtmaat AJ, Trachtenberg JT, Wilbrecht L, et al. (January 2005). "Transient and persistent dendritic spines in the neocortex in vivo". Neuron. 45 (2): 279–91. doi: 10.1016/j.neuron.2005.01.003 . PMID   15664179. S2CID   13320649.
  12. Zuo Y, Lin A, Chang P, Gan WB (April 2005). "Development of long-term dendritic brain stability in diverse regions of cerebral cortex". Neuron. 46 (2): 181–9. doi: 10.1016/j.neuron.2005.04.001 . PMID   15848798. S2CID   16232150.
  13. 1 2 Greenough WT, Volkmar FR (August 1973). "Pattern of dendritic branching in occipital cortex of rats reared in complex environments". Exp. Neurol. 40 (2): 491–504. doi:10.1016/0014-4886(73)90090-3. PMID   4730268.
  14. 1 2 Landi S, Sale A, Berardi N, Viegi A, Maffei L, Cenni MC (January 2007). "Retinal functional development is sensitive to environmental enrichment: a role for BDNF". FASEB J. 21 (1): 130–9. doi: 10.1096/fj.06-6083com . PMID   17135370. S2CID   8897589.
  15. Volkmar FR, Greenough WT (June 1972). "Rearing complexity affects branching of dendrites in the visual cortex of the rat". Science. 176 (4042): 1445–7. Bibcode:1972Sci...176.1445V. doi:10.1126/science.176.4042.1445. PMID   5033647. S2CID   35027584.
  16. Wallace CS, Kilman VL, Withers GS, Greenough WT (July 1992). "Increases in dendritic length in occipital cortex after 4 days of differential housing in weanling rats". Behav. Neural Biol. 58 (1): 64–8. doi:10.1016/0163-1047(92)90937-Y. PMID   1417672.
  17. 1 2 Koe, A; Ashokan, A; Mitra, R (2016). "Short environmental enrichment in adulthood reverses anxiety and basolateral amygdala hypertrophy induced by maternal separation". Transl Psychiatry. 6 (2): e729. doi: 10.1038/tp.2015.217 . PMC   4872421 . PMID   26836417.
  18. 1 2 3 4 5 6 Sirevaag AM, Greenough WT (October 1987). "Differential rearing effects on rat visual cortex synapses. III. Neuronal and glial nuclei, boutons, dendrites, and capillaries". Brain Res. 424 (2): 320–32. doi:10.1016/0006-8993(87)91477-6. PMID   3676831. S2CID   20782513.
  19. Sirevaag AM, Greenough WT (April 1985). "Differential rearing effects on rat visual cortex synapses. II. Synaptic morphometry". Brain Res. 351 (2): 215–26. doi:10.1016/0165-3806(85)90193-2. PMID   3995348.
  20. Shinohara Y, Hosoya A, Hirase H (April 2013). "Experience enhances gamma oscillations and interhemispheric asymmetry in the hippocampus". Nat Commun. 4 (4): 1652. Bibcode:2013NatCo...4.1652S. doi:10.1038/ncomms2658. PMC   3644069 . PMID   23552067.
  21. Jones TA, Greenough WT (January 1996). "Ultrastructural evidence for increased contact between astrocytes and synapses in rats reared in a complex environment". Neurobiol Learn Mem. 65 (1): 48–56. doi:10.1006/nlme.1996.0005. PMID   8673406. S2CID   45890185.
  22. Borowsky IW, Collins RC (October 1989). "Metabolic anatomy of brain: a comparison of regional capillary density, glucose metabolism, and enzyme activities". J. Comp. Neurol. 288 (3): 401–13. doi:10.1002/cne.902880304. PMID   2551935. S2CID   37188261.
  23. Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WT (July 1990). "Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats". Proc. Natl. Acad. Sci. U.S.A. 87 (14): 5568–72. Bibcode:1990PNAS...87.5568B. doi: 10.1073/pnas.87.14.5568 . PMC   54366 . PMID   1695380.
  24. Kleim JA, Hogg TM, VandenBerg PM, Cooper NR, Bruneau R, Remple M (January 2004). "Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning". J. Neurosci. 24 (3): 628–33. doi:10.1523/JNEUROSCI.3440-03.2004. PMC   6729261 . PMID   14736848.
  25. Sale A, Cenni MC, Ciucci F, Putignano E, Chierzi S, Maffei L (2007). Reh T (ed.). "Maternal Enrichment during Pregnancy Accelerates Retinal Development of the Fetus". PLOS ONE. 2 (11): e1160. Bibcode:2007PLoSO...2.1160S. doi: 10.1371/journal.pone.0001160 . PMC   2063464 . PMID   18000533. Open Access logo PLoS transparent.svg
  26. Fan Y, Liu Z, Weinstein PR, Fike JR, Liu J (January 2007). "Environmental enrichment enhances neurogenesis and improves functional outcome after cranial irradiation". Eur. J. Neurosci. 25 (1): 38–46. doi:10.1111/j.1460-9568.2006.05269.x. PMID   17241265. S2CID   43259184.
  27. Veena J, Srikumar BN, Mahati K, Bhagya V, Raju TR, Shankaranarayana Rao BS (March 2009). "Enriched environment restores hippocampal cell proliferation and ameliorates cognitive deficits in chronically stressed rats". J. Neurosci. Res. 87 (4): 831–43. doi:10.1002/jnr.21907. PMID   19006089. S2CID   21765537.
  28. Meshi D, Drew MR, Saxe M, et al. (June 2006). "Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment". Nat. Neurosci. 9 (6): 729–31. doi:10.1038/nn1696. PMID   16648847. S2CID   11043203.
  29. Rampon C, Jiang CH, Dong H, et al. (November 2000). "Effects of environmental enrichment on gene expression in the brain". Proc. Natl. Acad. Sci. U.S.A. 97 (23): 12880–4. Bibcode:2000PNAS...9712880R. doi: 10.1073/pnas.97.23.12880 . PMC   18858 . PMID   11070096.
  30. Ickes BR, Pham TM, Sanders LA, Albeck DS, Mohammed AH, Granholm AC (July 2000). "Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain". Exp. Neurol. 164 (1): 45–52. doi:10.1006/exnr.2000.7415. PMID   10877914. S2CID   24876134.
  31. 1 2 Torasdotter M, Metsis M, Henriksson BG, Winblad B, Mohammed AH (June 1998). "Environmental enrichment results in higher levels of nerve growth factor mRNA in the rat visual cortex and hippocampus". Behav. Brain Res. 93 (1–2): 83–90. doi:10.1016/S0166-4328(97)00142-3. PMID   9659990. S2CID   4022222.
  32. Zhu SW, Codita A, Bogdanovic N, et al. (February 2009). "Influence of environmental manipulation on exploratory behaviour in male BDNF knockout mice". Behav. Brain Res. 197 (2): 339–46. doi:10.1016/j.bbr.2008.09.032. PMID   18951926. S2CID   46218238.
  33. Rasmuson S, Olsson T, Henriksson BG, et al. (January 1998). "Environmental enrichment selectively increases 5-HT1A receptor mRNA expression and binding in the rat hippocampus". Brain Res. Mol. Brain Res. 53 (1–2): 285–90. doi:10.1016/S0169-328X(97)00317-3. PMID   9473697.
  34. Escorihuela RM, Fernández-Teruel A, Tobeña A, et al. (July 1995). "Early environmental stimulation produces long-lasting changes on beta-adrenoceptor transduction system". Neurobiol Learn Mem. 64 (1): 49–57. doi:10.1006/nlme.1995.1043. PMID   7582812. S2CID   26095038.
  35. Nithianantharajah J, Levis H, Murphy M (May 2004). "Environmental enrichment results in cortical and subcortical changes in levels of synaptophysin and PSD-95 proteins". Neurobiol Learn Mem. 81 (3): 200–10. doi:10.1016/j.nlm.2004.02.002. PMID   15082021. S2CID   27246269.
  36. Gogolla N, Galimberti I, Deguchi Y, Caroni P (May 2009). "Wnt signaling mediates experience-related regulation of synapse numbers and mossy fiber connectivities in the adult hippocampus". Neuron. 62 (4): 510–25. doi: 10.1016/j.neuron.2009.04.022 . PMID   19477153. S2CID   17085834.
  37. During MJ, Cao L (February 2006). "VEGF, a mediator of the effect of experience on hippocampal neurogenesis". Curr Alzheimer Res. 3 (1): 29–33. doi:10.2174/156720506775697133. PMID   16472200. Archived from the original on 2012-07-22.{{cite journal}}: CS1 maint: unfit URL (link)
  38. 1 2 Woo CC, Leon M (March 2011). "Environmental Enrichment as an Effective Treatment for Autism: A Randomized Controlled Trial". Behav Neurosci. 127 (4): 487–97. doi:10.1037/a0033010. PMID   23688137.
  39. Woo, Cynthia C.; Donnelly, Joseph H.; Steinberg-Epstein, Robin; Leon, Michael (Aug 2015). "Environmental enrichment as a therapy for autism: A clinical trial replication and extension". Behavioral Neuroscience. 129 (4): 412–422. doi:10.1037/bne0000068. PMC   4682896 . PMID   26052790.
  40. Mary Brophy Marcus (June 5, 2013). "'Sensory-Focused' Autism Therapy Shows Early Promise". webmd.com.
  41. Nkoyo Iyamba (October 9, 2014). "Autism treatment gives Utah family hope". ksl.com. Archived from the original on September 25, 2015.
  42. Berardi N, Braschi C, Capsoni S, Cattaneo A, Maffei L (June 2007). "Environmental enrichment delays the onset of memory deficits and reduces neuropathological hallmarks in a mouse model of Alzheimer-like neurodegeneration". J. Alzheimers Dis. 11 (3): 359–70. doi:10.3233/JAD-2007-11312. PMID   17851186. Archived from the original on 2012-07-20.
  43. Verret L, Krezymon A, Halley H, Trouche S, Zerwas M, Lazouret M, Lassalle JM, Rampon C (Jan 2013). "Transient enriched housing before amyloidosis onset sustains cognitive improvement in Tg2576 mice". Neurobiology of Aging. 34 (1): 211–25. doi:10.1016/j.neurobiolaging.2012.05.013. PMID   22727275. S2CID   28453351.
  44. Bourdon E, Belmin J (Jun 2021). "Enriched gardens improve cognition and independence of nursing home residents with dementia: a pilot controlled trial". Alzheimer's Research & Therapy. 13 (1): 116. doi: 10.1186/s13195-021-00849-w . PMC   8207740 . PMID   34134758. S2CID   235454186.
  45. 1 2 Spires TL, Grote HE, Varshney NK, et al. (March 2004). "Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism". J. Neurosci. 24 (9): 2270–6. doi:10.1523/JNEUROSCI.1658-03.2004. PMC   6730435 . PMID   14999077.
  46. Faherty CJ, Raviie Shepherd K, Herasimtschuk A, Smeyne RJ (March 2005). "Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism". Brain Res. Mol. Brain Res. 134 (1): 170–9. doi:10.1016/j.molbrainres.2004.08.008. PMID   15790541.
  47. 1 2 Goldberg, NR; Fields, V; Pflibsen, L; Salvatore, MF; Meshul, CK (March 2012). "Social enrichment attenuates nigrostriatal lesioning and reverses motor impairment in a progressive 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease". Neurobiology of Disease. 45 (3): 1051–67. doi:10.1016/j.nbd.2011.12.024. PMID   22198503. S2CID   32701524.
  48. Janssen H, Bernhardt J, Collier JM, Sena ES, McElduff P, Attia J, Pollack M, Howells DW, Nilsson M, Calford MB, Spratt NJ (12 September 2010). "An Enriched Environment Improves Sensorimotor Function Post-Ischemic Stroke" (PDF). Neurorehabilitation and Neural Repair. 24 (9): 802–813. doi:10.1177/1545968310372092. hdl:20.500.11820/302d9858-29ae-4a10-b684-e5f54bdb7ed9. PMID   20834046. S2CID   12755512.
  49. Janssen, Heidi; Ada, Louise; Bernhardt, Julie; McElduff, Patrick; Pollack, Michael; Nilsson, Michael; Spratt, Neil J. (29 April 2013). "An enriched environment increases activity in stroke patients undergoing rehabilitation in a mixed rehabilitation unit: a pilot non-randomized controlled trial". Disability and Rehabilitation. 36 (3): 255–262. doi:10.3109/09638288.2013.788218. PMID   23627534. S2CID   40609997.
  50. 1 2 Kondo M, Gray LJ, Pelka GJ, Christodoulou J, Tam PP, Hannan AJ (June 2008). "Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome--Mecp2 gene dosage effects and BDNF expression". Eur. J. Neurosci. 27 (12): 3342–50. doi:10.1111/j.1460-9568.2008.06305.x. PMID   18557922. S2CID   15401209.
  51. 1 2 Sale A, Maya Vetencourt JF, Medini P, et al. (June 2007). "Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition". Nat. Neurosci. 10 (6): 679–81. doi:10.1038/nn1899. PMID   17468749. S2CID   37390442.
  52. Argandoña EG, Bengoetxea H, Lafuente JV (2009). "Physical exercise is required for environmental enrichment to offset the quantitative effects of dark-rearing on the S-100β astrocytic density in the rat visual cortex". Journal of Anatomy. 215 (2): 132–140. doi:10.1111/j.1469-7580.2009.01103.x. PMC   2740960 . PMID   19500177.
  53. 1 2 Cao, Xiujing; Huang, Shenghai; Ruan, Diyun (April 2008). "Enriched environment restores impaired hippocampal long-term potentiation and water maze performance induced by developmental lead exposure in rats". Developmental Psychobiology. 50 (3): 307–313. doi:10.1002/dev.20287. PMID   18335502.
  54. 1 2 Fischer FR, Peduzzi JD (2007). "Functional Recovery in Rats With Chronic Spinal Cord Injuries After Exposure to an Enriched Environment". J Spinal Cord Med. 30 (2): 147–55. doi:10.1080/10790268.2007.11753926. PMC   2031947 . PMID   17591227.
  55. 1 2 Francis DD, Diorio J, Plotsky PM, Meaney MJ (September 2002). "Environmental enrichment reverses the effects of maternal separation on stress reactivity". J. Neurosci. 22 (18): 7840–3. doi:10.1523/JNEUROSCI.22-18-07840.2002. PMC   6758090 . PMID   12223535.
  56. 1 2 Bredy TW, Humpartzoomian RA, Cain DP, Meaney MJ (2003). "Partial reversal of the effect of maternal care on cognitive function through environmental enrichment". Neuroscience. 118 (2): 571–6. doi:10.1016/S0306-4522(02)00918-1. PMID   12699791. S2CID   46611492.
  57. 1 2 Speisman, RB; Kumar, A; Rani, A; Pastoriza, JM; Severance, JE; Foster, TC; Ormerod, BK (January 2013). "Environmental enrichment restores neurogenesis and rapid acquisition in aged rats". Neurobiology of Aging. 34 (1): 263–74. doi:10.1016/j.neurobiolaging.2012.05.023. PMC   3480541 . PMID   22795793.
  58. 1 2 Solinas M, Thiriet N, El Rawas R, Lardeux V, Jaber M (April 2009). "Environmental enrichment during early stages of life reduces the behavioral, neurochemical, and molecular effects of cocaine". Neuropsychopharmacology. 34 (5): 1102–11. doi: 10.1038/npp.2008.51 . PMID   18463628.
  59. Kozorovitskiy Y, Gross CG, Kopil C, et al. (November 2005). "Experience induces structural and biochemical changes in the adult primate brain". Proc. Natl. Acad. Sci. U.S.A. 102 (48): 17478–82. Bibcode:2005PNAS..10217478K. doi: 10.1073/pnas.0508817102 . PMC   1297690 . PMID   16299105.
  60. Jacobs B, Schall M, Scheibel AB (January 1993). "A quantitative dendritic analysis of Wernicke's area in humans. II. Gender, hemispheric, and environmental factors". J. Comp. Neurol. 327 (1): 97–111. doi:10.1002/cne.903270108. PMID   8432910. S2CID   2084006.
  61. Ilg R, Wohlschläger AM, Gaser C, et al. (April 2008). "Gray matter increase induced by practice correlates with task-specific activation: a combined functional and morphometric magnetic resonance imaging study". J. Neurosci. 28 (16): 4210–5. doi:10.1523/JNEUROSCI.5722-07.2008. PMC   6670304 . PMID   18417700.
  62. Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, May A (January 2004). "Neuroplasticity: changes in grey matter induced by training". Nature. 427 (6972): 311–2. Bibcode:2004Natur.427..311D. doi:10.1038/427311a. PMID   14737157. S2CID   4421248.
  63. Draganski B, Gaser C, Kempermann G, et al. (June 2006). "Temporal and spatial dynamics of brain structure changes during extensive learning". J. Neurosci. 26 (23): 6314–7. doi:10.1523/JNEUROSCI.4628-05.2006. PMC   6675198 . PMID   16763039.
  64. Kaler SR, Freeman BJ (May 1994). "Analysis of environmental deprivation: cognitive and social development in Romanian orphans". J Child Psychol Psychiatry. 35 (4): 769–81. doi:10.1111/j.1469-7610.1994.tb01220.x. PMID   7518826.
  65. Rutter M, Andersen-Wood L, Beckett C, et al. (May 1999). "Quasi-autistic patterns following severe early global privation. English and Romanian Adoptees (ERA) Study Team". J Child Psychol Psychiatry. 40 (4): 537–49. doi:10.1017/S0021963099003935. PMID   10357161.
  66. Windsor J, Glaze LE, Koga SF (October 2007). "Language acquisition with limited input: Romanian institution and foster care". J. Speech Lang. Hear. Res. 50 (5): 1365–81. doi:10.1044/1092-4388(2007/095). PMID   17905917.
  67. Beckett C, Maughan B, Rutter M, et al. (2006). "Do the effects of early severe deprivation on cognition persist into early adolescence? Findings from the English and Romanian adoptees study". Child Dev. 77 (3): 696–711. doi:10.1111/j.1467-8624.2006.00898.x. PMID   16686796.
  68. Chugani HT, Behen ME, Muzik O, Juhász C, Nagy F, Chugani DC (December 2001). "Local brain functional activity following early deprivation: a study of postinstitutionalized Romanian orphans". NeuroImage. 14 (6): 1290–301. doi:10.1006/nimg.2001.0917. PMID   11707085. S2CID   30892.
  69. Eluvathingal TJ, Chugani HT, Behen ME, et al. (June 2006). "Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study". Pediatrics. 117 (6): 2093–100. doi:10.1542/peds.2005-1727. PMID   16740852. S2CID   30359252.
  70. Guzzetta A, Baldini S, Bancale A, et al. (May 2009). "Massage accelerates brain development and the maturation of visual function". J. Neurosci. 29 (18): 6042–51. doi:10.1523/JNEUROSCI.5548-08.2009. PMC   6665233 . PMID   19420271.
  71. Wilson R, Barnes L, Bennett D (August 2003). "Assessment of lifetime participation in cognitively stimulating activities". J Clin Exp Neuropsychol. 25 (5): 634–42. doi:10.1076/jcen.25.5.634.14572. PMID   12815501. S2CID   11877167.
  72. Corral M, Rodríguez M, Amenedo E, Sánchez JL, Díaz F (2006). "Cognitive reserve, age, and neuropsychological performance in healthy participants". Dev Neuropsychol. 29 (3): 479–91. doi:10.1207/s15326942dn2903_6. PMID   16671863. S2CID   27689165.
  73. Fritsch T, McClendon MJ, Smyth KA, Lerner AJ, Friedland RP, Larsen JD (June 2007). "Cognitive functioning in healthy aging: the role of reserve and lifestyle factors early in life". Gerontologist. 47 (3): 307–22. doi: 10.1093/geront/47.3.307 . PMID   17565095.
  74. Hall CB, Derby C, LeValley A, Katz MJ, Verghese J, Lipton RB (October 2007). "Education delays accelerated decline on a memory test in persons who develop dementia". Neurology. 69 (17): 1657–64. doi:10.1212/01.wnl.0000278163.82636.30. PMID   17954781. S2CID   33173284.
  75. Nebes RD, Meltzer CC, Whyte EM, et al. (2006). "The relation of white matter hyperintensities to cognitive performance in the normal old: education matters". Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 13 (3–4): 326–40. doi:10.1080/138255890969294. PMID   16887777. S2CID   20341312.
  76. Elkins JS, Longstreth WT, Manolio TA, Newman AB, Bhadelia RA, Johnston SC (August 2006). "Education and the cognitive decline associated with MRI-defined brain infarct". Neurology. 67 (3): 435–40. doi:10.1212/01.wnl.0000228246.89109.98. PMID   16894104. S2CID   44570701.
  77. Koepsell TD, Kurland BF, Harel O, Johnson EA, Zhou XH, Kukull WA (May 2008). "Education, cognitive function, and severity of neuropathology in Alzheimer disease". Neurology. 70 (19 Pt 2): 1732–9. doi:10.1212/01.wnl.0000284603.85621.aa. PMID   18160675. S2CID   31439417.
  78. Roe CM, Mintun MA, D'Angelo G, Xiong C, Grant EA, Morris JC (November 2008). "Alzheimer's and Cognitive Reserve: Education Effect Varies with 11CPIB Uptake". Arch. Neurol. 65 (11): 1467–71. doi:10.1001/archneur.65.11.1467. PMC   2752218 . PMID   19001165.
  79. Kesler SR, Adams HF, Blasey CM, Bigler ED (2003). "Premorbid intellectual functioning, education, and brain size in traumatic brain injury: an investigation of the cognitive reserve hypothesis". Appl Neuropsychol. 10 (3): 153–62. doi:10.1207/S15324826AN1003_04. PMID   12890641. S2CID   23635493.
  80. Fratiglioni L, Paillard-Borg S, Winblad B (June 2004). "An active and socially integrated lifestyle in late life might protect against dementia". Lancet Neurol. 3 (6): 343–53. doi:10.1016/S1474-4422(04)00767-7. PMID   15157849. S2CID   8818506.
  81. Pai MC, Tsai JJ (2005). "Is cognitive reserve applicable to epilepsy? The effect of educational level on the cognitive decline after onset of epilepsy". Epilepsia. 46 (Suppl 1): 7–10. doi:10.1111/j.0013-9580.2005.461003.x. PMID   15816971. S2CID   24313873.

Bibliography

Related Research Articles

<span class="mw-page-title-main">Hippocampus</span> Vertebrate brain region involved in memory consolidation

The hippocampus is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located in the allocortex, with neural projections into the neocortex, in humans as well as other primates. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In humans, it contains two main interlocking parts: the hippocampus proper, and the dentate gyrus.

<span class="mw-page-title-main">Long-term potentiation</span> Persistent strengthening of synapses based on recent patterns of activity

In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons. The opposite of LTP is long-term depression, which produces a long-lasting decrease in synaptic strength.

<span class="mw-page-title-main">Olfactory bulb</span> Neural structure

The olfactory bulb is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OFC) and the hippocampus where it plays a role in emotion, memory and learning.

In neurophysiology, long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress.

<span class="mw-page-title-main">Glia</span> Support cells in the nervous system

Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system and the peripheral nervous system that do not produce electrical impulses. The neuroglia make up more than one half the volume of neural tissue in the human body. They maintain homeostasis, form myelin in the peripheral nervous system, and provide support and protection for neurons. In the central nervous system, glial cells include oligodendrocytes, astrocytes, ependymal cells and microglia, and in the peripheral nervous system they include Schwann cells and satellite cells.

<span class="mw-page-title-main">Brain-derived neurotrophic factor</span> Protein found in humans

Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen.

<span class="mw-page-title-main">Adult neurogenesis</span> Generating of neurons from neural stem cells in adults

Adult neurogenesis is the process in which neurons are generated from neural stem cells in the adult. This process differs from prenatal neurogenesis.

<span class="mw-page-title-main">Locus coeruleus</span> Stress and panic response centre

The locus coeruleus (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system.

<span class="mw-page-title-main">Astrocyte</span> Type of brain cell

Astrocytes, also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to around 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system. Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. Astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses.

Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.

<span class="mw-page-title-main">Barrel cortex</span> Region of the somatosensory cortex in some rodents and other species

The barrel cortex is a region of the somatosensory cortex that is identifiable in some species of rodents and species of at least two other orders and contains the barrel field. The 'barrels' of the barrel field are regions within cortical layer IV that are visibly darker when stained to reveal the presence of cytochrome c oxidase and are separated from each other by lighter areas called septa. These dark-staining regions are a major target for somatosensory inputs from the thalamus, and each barrel corresponds to a region of the body. Due to this distinctive cellular structure, organisation, and functional significance, the barrel cortex is a useful tool to understand cortical processing and has played an important role in neuroscience. The majority of what is known about corticothalamic processing comes from studying the barrel cortex, and researchers have intensively studied the barrel cortex as a model of neocortical column.

Neuroplasticity, also known as neural plasticity or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it previously functioned. These changes range from individual neuron pathways making new connections, to systematic adjustments like cortical remapping or neural oscillation. Other forms of neuroplasticity include homologous area adaptation, cross modal reassignment, map expansion, and compensatory masquerade. Examples of neuroplasticity include circuit and network changes that result from learning a new ability, information acquisition, environmental influences, pregnancy, caloric intake, practice/training, and psychological stress.

<span class="mw-page-title-main">CX614</span> Chemical compound

CX-614 is an ampakine drug developed by Cortex Pharmaceuticals. It has been investigated for its effect on AMPA receptors.

<span class="mw-page-title-main">Perineuronal net</span> Structures of the brain

Perineuronal nets (PNNs) are specialized extracellular matrix structures responsible for synaptic stabilization in the adult brain. PNNs are found around certain neuron cell bodies and proximal neurites in the central nervous system. PNNs play a critical role in the closure of the childhood critical period, and their digestion can cause restored critical period-like synaptic plasticity in the adult brain. They are largely negatively charged and composed of chondroitin sulfate proteoglycans, molecules that play a key role in development and plasticity during postnatal development and in the adult.

Activity-dependent plasticity is a form of functional and structural neuroplasticity that arises from the use of cognitive functions and personal experience; hence, it is the biological basis for learning and the formation of new memories. Activity-dependent plasticity is a form of neuroplasticity that arises from intrinsic or endogenous activity, as opposed to forms of neuroplasticity that arise from extrinsic or exogenous factors, such as electrical brain stimulation- or drug-induced neuroplasticity. The brain's ability to remodel itself forms the basis of the brain's capacity to retain memories, improve motor function, and enhance comprehension and speech amongst other things. It is this trait to retain and form memories that is associated with neural plasticity and therefore many of the functions individuals perform on a daily basis. This plasticity occurs as a result of changes in gene expression which are triggered by signaling cascades that are activated by various signaling molecules during increased neuronal activity.

<span class="mw-page-title-main">Neurobiological effects of physical exercise</span> Neural, cognitive, and behavioral effects of physical exercise

The neurobiological effects of physical exercise involve possible interrelated effects on brain structure, brain function, and cognition. Research in humans has demonstrated that consistent aerobic exercise may induce improvements in certain cognitive functions, neuroplasticity and behavioral plasticity; some of these long-term effects may include increased neuron growth, increased neurological activity, improved stress coping, enhanced cognitive control of behavior, improved declarative, spatial, and working memory, and structural and functional improvements in brain structures and pathways associated with cognitive control and memory. The effects of exercise on cognition may affect academic performance in children and college students, improve adult productivity, preserve cognitive function in old age, preventing or treating certain neurological disorders, and improving overall quality of life.

While the cellular and molecular mechanisms of learning and memory have long been a central focus of neuroscience, it is only in recent years that attention has turned to the epigenetic mechanisms behind the dynamic changes in gene transcription responsible for memory formation and maintenance. Epigenetic gene regulation often involves the physical marking of DNA or associated proteins to cause or allow long-lasting changes in gene activity. Epigenetic mechanisms such as DNA methylation and histone modifications have been shown to play an important role in learning and memory.

Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences. The process of developing an addiction occurs through instrumental learning, which is otherwise known as operant conditioning.

Epigenetics of depression is the study of how epigenetics contribute to depression.

<span class="mw-page-title-main">ANA-12</span> Chemical compound

ANA-12 is a selective, small-molecule non-competitive antagonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF). ANA-12 was originally discovered and developed by Cazorla M. and colleagues at Université Paris and Inserm in 2011. The compound crosses the blood-brain-barrier and exerts central TrkB blockade, producing effects as early as 30 minutes and as long as 6 hours following intraperitoneal injection in mice. It blocks the neurotrophic actions of BDNF without compromising neuron survival.