Medium spiny neuron

Last updated

Medium spiny neuron
Details
Location Basal ganglia
ShapeSpiny neuron
FunctionInhibitory projection neuron
Neurotransmitter GABA
Presynaptic connectionsDopaminergic: VTA, SNc
Glutamatergic: PFC, hippocampus, amygdala, thalamus, other
Postsynaptic connectionsOther basal ganglia structures
Identifiers
MeSH D000094242
NeuroLex ID nifext_141
Anatomical terms of neuroanatomy

Medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), are a special type of GABAergic inhibitory cell representing 95% of neurons within the human striatum, a basal ganglia structure. [1] Medium spiny neurons have two primary phenotypes (characteristic types): D1-type MSNs of the direct pathway and D2-type MSNs of the indirect pathway. [1] [2] [3] Most striatal MSNs contain only D1-type or D2-type dopamine receptors, but a subpopulation of MSNs exhibit both phenotypes. [1] [2] [3]

Contents

Direct pathway MSNs excite their ultimate basal ganglia output structure (such as the thalamus) and promote associated behaviors; [1] these neurons express D1-type dopamine receptors, adenosine A1 receptors, dynorphin peptides, and substance P peptides. [1] [2] Indirect pathway MSNs inhibit their output structure and in turn inhibit associated behaviors; [1] these neurons express D2-type dopamine receptors, adenosine A2A receptors (A2A), DRD2–A2A heterotetramers, and enkephalin. [2] [4] Both types express glutamate receptors (NMDAR and AMPAR), cholinergic receptors (M1 and M4) [5] and CB1 receptors are expressed on the somatodendritic area of both MSN types. [2] [6] A subpopulation of MSNs contain both D1-type and D2-type receptors, with approximately 40% of striatal MSNs expressing both DRD1 and DRD2 mRNA. [1] [2] [3] In the nucleus accumbens (NAcc), these mixed-type MSNs that contain both D1-type and D2-type receptors are mostly contained in the NAcc shell. [1]

The dorsal striatal MSNs play a key role in initiating and controlling movements of the body, limbs, and eyes. The ventral striatal MSNs play a key role in motivation, reward, reinforcement, and aversion. Dorsal and ventral medium spiny neuron subtypes (i.e., direct D1-type and indirect D2-type) are identical phenotypes, but their output connections differ. [1] [2]

Confocal microscopy Z projection of medium spiny neurons (MSNs) in the mouse striatum. The neurons were labeled using the matrisome MSN mouse Gpr101-Cre in combination with a dtTomato (red fluorescent protein) reporter. A 3D projection of the same neurons can be viewed here. Z MaxProjection of MediumSpinyNeurons Gpr101Cre dtTomato.jpg
Confocal microscopy Z projection of medium spiny neurons (MSNs) in the mouse striatum. The neurons were labeled using the matrisome MSN mouse Gpr101-Cre in combination with a dtTomato (red fluorescent protein) reporter. A 3D projection of the same neurons can be viewed here.

Appearance and location

The medium spiny neurons are medium-sized neurons (~15 microns in diameter, ~12–13 microns in the mouse) with large and extensive dendritic trees (~500 microns in diameter). [8] Striatal direct pathway MSNs (dMSNs) project directly to the globus pallidus internal (GPi) and substantia nigra pars reticulata (SNpr) whereas striatal indirect pathway MSNs (iMSNs) ultimately project to these two structures via an intermediate connection to the globus pallidus external (GPe) and ventral pallidum (VP). [1] The GPe and VP send a GABAergic projection to the subthalamic nucleus, which then sends glutamatergic projections to the GPi and SNpr. [1] Both the GPi and SNpr send inhibitory projections to nuclei within the thalamus. [1]

Function

MSNs are inhibitory GABAergic neurons, but the effect of direct MSNs (dMSNs) and indirect MSNs (iMSNs) on their ultimate output structures differs: dMSNs excite, while iMSNs inhibit, their basal ganglia output structures (e.g., the thalamus). [1] Within the basal ganglia, there are several complex circuits of neuronal loops all of which include medium spiny neurons.

The cortical, thalamic, and brain-stem inputs that arrive at the medium spiny neurons show a vast divergence in that each incoming axon forms contacts with many spiny neurons and each spiny neuron receives a vast amount of input from different incoming axons. Since these inputs are glutamatergic they exhibit an excitatory influence on the inhibitory medium spiny neurons.

There are also interneurons in the striatum which regulate the excitability of the medium spiny neurons. The synaptic connections between a particular GABAergic interneuron, the parvalbumin expressing fast-spiking interneuron, and spiny neurons are close to the spiny neurons' soma, or cell body. [9] Recall that excitatory postsynaptic potentials caused by glutamatergic inputs at the dendrites of the spiny neurons only cause an action potential when the depolarization wave is strong enough upon entering the cell soma. Since the fast-spiking interneurons influence is located so closely to this critical gate between the dendrites and the soma, they can readily regulate the generation of an action potential. Additionally, other types of GABAergic interneurons make connections with the spiny neurons. These include interneurons that express tyrosine hydroxylase [10] [11] and neuropeptide Y. [12] [13]

Dorsal striatal MSNs

Direct pathway

Anatomy

The direct pathway within the basal ganglia receives excitatory input from the cortex, thalamus, and other brain regions. In the direct pathway, medium spiny neurons project to the internal division of the globus pallidus (GPi) or the substantia nigra pars reticula (SNpr or SNr). These nuclei project to the deep layer of the superior colliculus and control fast eye movements (saccades), [14] and also project to the ventral thalamus, which in turn projects to upper motor neurons in the primary motor cortex (precentral gyrus). [15] The SNr and GPi outputs are both tonically active inhibitory nuclei and are thus constantly inhibiting the thalamus (and thus motor cortex). However, transient activity in (inhibitory) direct pathway medium spiny neurons ultimately disinhibits thalamus projections to the motor cortex and enables movement. [16]

Indirect pathway

Anatomy

The indirect pathway also receives excitatory input from various brain regions. Indirect pathway medium spiny neurons project to the external segment of the globus pallidus (GPe). Like the GPi, the GPe is a tonically active inhibitory nucleus. The GPe projects to the excitatory subthalamic nucleus (STN), which in turn projects to the GPi and SNr. [15] When the indirect pathway is not activated, activity in the STN is suppressed by the GPe, which translates to decreased SNr/GPi activity downstream and thus increased thalamic and motor cortex neuron activity. When indirect pathway neurons fire, GPe neurons are inhibited, which disinhibits the STN. The STN then excites SNr/GPi neurons, suppressing thalamus/motor cortex activity. [16]

Functional distinctions

Classic models of striatal function have posited that activation of the direct pathway leads to movement, whereas activation of the indirect pathway leads to the termination of movement. [17] [18] This model is supported by experiments demonstrating that optogenetically stimulating direct pathway medium spiny neurons increases locomotion, whereas stimulating indirect pathway medium spiny neurons inhibits locomotion. [19] The balance of direct/indirect activity in movement is supported by evidence from neurodegenerative disorders, including Parkinson's disease (PD), which is characterized by loss of dopamine neurons projecting to the striatum, hypoactivity in direct pathway and hyperactivity in indirect pathway neurons, along with motor dysfunction. [20] This results in loss of normal action selection, as loss of dopamine drives activity in the indirect pathway, globally inhibiting all motor paradigms. This may explain impaired action initiation, slowed actions (bradykinesia), and impaired voluntary motor initiation in Parkinson's patients. On the other hand, Huntington's disease, which is characterized by preferential degradation of indirect pathway medium spiny neurons, results in unwanted movements (chorea) that may result from impaired movement inhibition and predominant direct pathway activity. [21] An alternative related hypothesis is that the striatum controls action initiation and selection via a ’center-surround’ architecture, where activation of a subset of direct pathway neurons initiates movements while closely related motor patterns represented by surrounding neurons are inhibited by lateral inhibition via indirect pathway neurons. [22] This specific hypothesis is supported by recent calcium-imaging work showing that direct and indirect pathway medium spiny neurons encoding specific actions are located in spatially organized ensembles. [23]

Despite the abundance of evidence for the initiation/termination model, recent evidence using transgenic mice expressing calcium indicators in either the direct or indirect pathway demonstrated that both pathways are active at action initiation, but neither are active during inactivity, [24] a finding which has been replicated using simultaneous two-channel calcium imaging. [25] This has led to somewhat of a paradigm shift in models of striatal functioning, such that newer models posit that the direct pathway facilitates wanted movements, whereas the indirect pathway simultaneously inhibits unwanted movements. [26] [27] Indeed, more sophisticated techniques and analyses, such as state-dependent optogenetics, have revealed that both pathways are heavily involved in action sequence execution, [28] and that specifically, both striatal pathways are involved in element-level action control. [29] However, direct pathway medium spiny neurons mostly signal sequence initiation/termination and indirect pathway medium spiny neurons may signal switching between subsequences of a given action sequence. [30] Other evidence suggests that the direct and indirect pathway oppositely influence the termination of movement—specifically, the relative timing of their activity determines if an action will be terminated. [31]

Recent experiments have established that the direct and indirect pathways of the dorsal striatum are not solely involved in movement. Initial experiments in an intracranial self-stimulation paradigm suggested opposing roles in reinforcement for the two pathways; specifically, stimulation of direct pathway medium spiny neurons was found to be reinforcing, whereas stimulation of indirect pathway medium spiny neurons was aversive. [32] However, a subsequent study (using more physiologically relevant stimulation parameters) found that direct and indirect pathway stimulation was reinforcing, but that pathway-specific stimulation resulted in the development of different action strategies. [33] Regardless, these studies suggest a critical role for reinforcement in the dorsal striatum, as opposed to the striatum only serving a role in movement control.

Ventral striatal MSNs

Direct pathway

The direct pathway of the ventral striatum within the basal ganglia mediates reward-based learning and appetitive incentive salience, which is assigned to rewarding stimuli. [34]

Indirect pathway

The indirect pathway of the ventral striatum within the basal ganglia mediates aversion-based learning and aversive motivational salience, which is assigned to aversive stimuli. [34]

Related Research Articles

<span class="mw-page-title-main">Striatum</span> Nucleus in the basal ganglia of the brain

The striatum, or corpus striatum, is a nucleus in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamatergic and dopaminergic inputs from different sources; and serves as the primary input to the rest of the basal ganglia.

<span class="mw-page-title-main">Substantia nigra</span> Structure in the basal ganglia of the brain

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

<span class="mw-page-title-main">Basal ganglia</span> Group of subcortical nuclei involved in the motor and reward systems

The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an external and internal region, and in the division of the striatum. The basal ganglia are situated at the base of the forebrain and top of the midbrain. Basal ganglia are strongly interconnected with the cerebral cortex, thalamus, and brainstem, as well as several other brain areas. The basal ganglia are associated with a variety of functions, including control of voluntary motor movements, procedural learning, habit learning, conditional learning, eye movements, cognition, and emotion.

The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ventral striatum includes the nucleus accumbens and the olfactory tubercle.

<span class="mw-page-title-main">Nucleus accumbens</span> Region of the basal forebrain

The nucleus accumbens is a region in the basal forebrain rostral to the preoptic area of the hypothalamus. The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum. The ventral striatum and dorsal striatum collectively form the striatum, which is the main component of the basal ganglia. The dopaminergic neurons of the mesolimbic pathway project onto the GABAergic medium spiny neurons of the nucleus accumbens and olfactory tubercle. Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.

<span class="mw-page-title-main">Dopaminergic pathways</span> Projection neurons in the brain that synthesize and release dopamine

Dopaminergic pathways in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons.

<span class="mw-page-title-main">Nigrostriatal pathway</span>

The nigrostriatal pathway is a bilateral dopaminergic pathway in the brain that connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum in the forebrain. It is one of the four major dopamine pathways in the brain, and is critical in the production of movement as part of a system called the basal ganglia motor loop. Dopaminergic neurons of this pathway release dopamine from axon terminals that synapse onto GABAergic medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), located in the striatum.

<span class="mw-page-title-main">Ventral tegmental area</span> Group of neurons on the floor of the midbrain

The ventral tegmental area (VTA), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways; it is widely implicated in the drug and natural reward circuitry of the brain. The VTA plays an important role in a number of processes, including reward cognition and orgasm, among others, as well as several psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the prefrontal cortex to the caudal brainstem and several regions in between.

<span class="mw-page-title-main">Subthalamic nucleus</span> Small lens-shaped nucleus in the brain

The subthalamic nucleus (STN) is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. In terms of anatomy, it is the major part of the subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also dorsal to the substantia nigra and medial to the internal capsule. It was first described by Jules Bernard Luys in 1865, and the term corpus Luysi or Luys' body is still sometimes used.

The pars reticulata (SNpr) is a portion of the substantia nigra and is located lateral to the pars compacta. Most of the neurons that project out of the pars reticulata are inhibitory GABAergic neurons.

<span class="mw-page-title-main">Primate basal ganglia</span>

The basal ganglia form a major brain system in all species of vertebrates, but in primates there are special features that justify a separate consideration. As in other vertebrates, the primate basal ganglia can be divided into striatal, pallidal, nigral, and subthalamic components. In primates, however, there are two pallidal subdivisions called the external globus pallidus (GPe) and internal globus pallidus (GPi). Also in primates, the dorsal striatum is divided by a large tract called the internal capsule into two masses named the caudate nucleus and the putamen—in most other species no such division exists, and only the striatum as a whole is recognized. Beyond this, there is a complex circuitry of connections between the striatum and cortex that is specific to primates. This complexity reflects the difference in functioning of different cortical areas in the primate brain.

<span class="mw-page-title-main">Reward system</span> Group of neural structures responsible for motivation and desire

The reward system is a group of neural structures responsible for incentive salience, associative learning, and positively-valenced emotions, particularly ones involving pleasure as a core component. Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. A rewarding stimulus has been described as "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward". In operant conditioning, rewarding stimuli function as positive reinforcers; however, the converse statement also holds true: positive reinforcers are rewarding.

<span class="mw-page-title-main">External globus pallidus</span>

The external globus pallidus combines with the internal globus pallidus (GPi) to form the globus pallidus, an anatomical subset of the basal ganglia. Globus pallidus means "pale globe" in Latin, indicating its appearance. The external globus pallidus is the segment of the globus pallidus that is relatively further (lateral) from the midline of the brain.

<span class="mw-page-title-main">Internal globus pallidus</span>

The internal globus pallidus and the external globus pallidus (GPe) make up the globus pallidus. The GPi is one of the output nuclei of the basal ganglia. The GABAergic neurons of the GPi send their axons to the ventral anterior nucleus (VA) and the ventral lateral nucleus (VL) in the dorsal thalamus, to the centromedian complex, and to the pedunculopontine complex.

<span class="mw-page-title-main">Ganglionic eminence</span>

The ganglionic eminence (GE) is a transitory structure in the development of the nervous system that guides cell and axon migration. It is present in the embryonic and fetal stages of neural development found between the thalamus and caudate nucleus.

<span class="mw-page-title-main">Basal ganglia disease</span> Group of physical problems resulting from basal ganglia dysfunction

Basal ganglia disease is a group of physical problems that occur when the group of nuclei in the brain known as the basal ganglia fail to properly suppress unwanted movements or to properly prime upper motor neuron circuits to initiate motor function. Research indicates that increased output of the basal ganglia inhibits thalamocortical projection neurons. Proper activation or deactivation of these neurons is an integral component for proper movement. If something causes too much basal ganglia output, then the ventral anterior (VA) and ventral lateral (VL) thalamocortical projection neurons become too inhibited, and one cannot initiate voluntary movement. These disorders are known as hypokinetic disorders. However, a disorder leading to abnormally low output of the basal ganglia leads to reduced inhibition, and thus excitation, of the thalamocortical projection neurons which synapse onto the cortex. This situation leads to an inability to suppress unwanted movements. These disorders are known as hyperkinetic disorders.

The ventral pallidum (VP) is a structure within the basal ganglia of the brain. It is an output nucleus whose fibres project to thalamic nuclei, such as the ventral anterior nucleus, the ventral lateral nucleus, and the medial dorsal nucleus. The VP is a core component of the reward system which forms part of the limbic loop of the basal ganglia, a pathway involved in the regulation of motivational salience, behavior, and emotions. It is involved in addiction.

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.

<span class="mw-page-title-main">Cortico-basal ganglia-thalamo-cortical loop</span> System of neural circuits in the brain

The cortico-basal ganglia-thalamo-cortical loop is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the cortex. It is of particular relevance to hyperkinetic and hypokinetic movement disorders, such as Parkinson's disease and Huntington's disease, as well as to mental disorders of control, such as attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and Tourette syndrome.

D. James "Jim" Surmeier, an American neuroscientist and physiologist of note, is the Nathan Smith Davis Professor and Chair in the Department of Physiology at Northwestern University Feinberg School of Medicine. His research is focused on the cellular physiology and circuit properties of the basal ganglia in health and disease, primarily Parkinson's and Huntington's disease as well as pain.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 Yager LM, Garcia AF, Wunsch AM, Ferguson SM (August 2015). "The ins and outs of the striatum: Role in drug addiction". Neuroscience. 301: 529–541. doi:10.1016/j.neuroscience.2015.06.033. PMC   4523218 . PMID   26116518. [The striatum] receives dopaminergic inputs from the ventral tegmental area (VTA) and the substantia nigra (SNr) and glutamatergic inputs from several areas, including the cortex, hippocampus, amygdala, and thalamus (Swanson, 1982; Phillipson and Griffiths, 1985; Finch, 1996; Groenewegen et al., 1999; Britt et al., 2012). These glutamatergic inputs make contact on the heads of dendritic spines of the striatal GABAergic medium spiny projection neurons (MSNs) whereas dopaminergic inputs synapse onto the spine neck, allowing for an important and complex interaction between these two inputs in modulation of MSN activity ... It should also be noted that there is a small population of neurons in the NAc that coexpress both D1 and D2 receptors, though this is largely restricted to the NAc shell (Bertran- Gonzalez et al., 2008). ... Neurons in the NAc core and NAc shell subdivisions also differ functionally. The NAc core is involved in the processing of conditioned stimuli whereas the NAc shell is more important in the processing of unconditioned stimuli; Classically, these two striatal MSN populations are thought to have opposing effects on basal ganglia output. Activation of the dMSNs causes a net excitation of the thalamus resulting in a positive cortical feedback loop; thereby acting as a 'go' signal to initiate behavior. Activation of the iMSNs, however, causes a net inhibition of thalamic activity resulting in a negative cortical feedback loop and therefore serves as a 'brake' to inhibit behavior ... there is also mounting evidence that iMSNs play a role in motivation and addiction (Lobo and Nestler, 2011; Grueter et al., 2013). For example, optogenetic activation of NAc core and shell iMSNs suppressed the development of a cocaine CPP whereas selective ablation of NAc core and shell iMSNs ... enhanced the development and the persistence of an amphetamine CPP (Durieux et al., 2009; Lobo et al., 2010). These findings suggest that iMSNs can bidirectionally modulate drug reward. ... Together these data suggest that iMSNs normally act to restrain drug-taking behavior and recruitment of these neurons may in fact be protective against the development of compulsive drug use.
  2. 1 2 3 4 5 6 7 Ferré S, Lluís C, Justinova Z, Quiroz C, Orru M, Navarro G, Canela EI, Franco R, Goldberg SR (June 2010). "Adenosine-cannabinoid receptor interactions. Implications for striatal function". Br. J. Pharmacol. 160 (3): 443–453. doi:10.1111/j.1476-5381.2010.00723.x. PMC   2931547 . PMID   20590556. Two classes of MSNs, which are homogeneously distributed in the striatum, can be differentiated by their output connectivity and their expression of dopamine and adenosine receptors and neuropeptides. In the dorsal striatum (mostly represented by the nucleus caudate-putamen), enkephalinergic MSNs connect the striatum with the globus pallidus (lateral globus pallidus) and express the peptide enkephalin and a high density of dopamine D2 and adenosine A2A receptors (they also express adenosine A1 receptors), while dynorphinergic MSNs connect the striatum with the substantia nigra (pars compacta and reticulata) and the entopeduncular nucleus (medial globus pallidus) and express the peptides dynorphin and substance P and dopamine D1 and adenosine A1 but not A2A receptors (Ferréet al., 1997; Gerfen, 2004; Quiroz et al., 2009). These two different phenotypes of MSN are also present in the ventral striatum (mostly represented by the nucleus accumbens and the olfactory tubercle). However, although they are phenotypically equal to their dorsal counterparts, they have some differences in terms of connectivity. First, not only enkephalinergic but also dynorphinergic MSNs project to the ventral counterpart of the lateral globus pallidus, the ventral pallidum, which, in fact, has characteristics of both the lateral and medial globus pallidus in its afferent and efferent connectivity. In addition to the ventral pallidum, the medial globus pallidus and the substantia nigra-VTA, the ventral striatum sends projections to the extended amygdala, the lateral hypothalamus and the pedunculopontine tegmental nucleus. Finally, unlike the dorsal striatum, the substantia nigra pars reticulata is not a main target area for the ventral striatum, which preferentially directs its midbrain output to the substantia nigra pars compacta and the VTA (Heimer et al., 1995; Robertson and Jian, 1995; Ferré, 1997). It is also important to mention that a small percentage of MSNs have a mixed phenotype and express both D1 and D2 receptors (Surmeier et al., 1996). ... A2A receptors are localized predominantly postsynaptically in the dendritic spine of enkephalinergic but not dynorphinergic MSNs, co-localized with D2 receptors  ... Presynaptically, CB1 receptors are localized in GABAergic terminals of interneurons or collaterals from MSNs, and also in glutamatergic but not in dopaminergic terminals ... Postsynaptically, CB1 receptors are localized in the somatodendritic area of MSN (Rodriguez et al., 2001; Pickel et al., 2004; 2006; Köfalvi et al., 2005) and both enkephalinergic and dynorphinergic MSNs express CB1 receptors (Martín et al., 2008).
  3. 1 2 3 Nishi A, Kuroiwa M, Shuto T (July 2011). "Mechanisms for the modulation of dopamine d(1) receptor signaling in striatal neurons". Front Neuroanat. 5: 43. doi: 10.3389/fnana.2011.00043 . PMC   3140648 . PMID   21811441. Dopamine plays critical roles in the regulation of psychomotor functions in the brain (Bromberg-Martin et al., 2010; Cools, 2011; Gerfen and Surmeier, 2011). The dopamine receptors are a superfamily of heptahelical G protein-coupled receptors, and are grouped into two categories, D1-like (D1, D5) and D2-like (D2, D3, D4) receptors, based on functional properties to stimulate adenylyl cyclase (AC) via Gs/olf and to inhibit AC via Gi/o, respectively ... It has been demonstrated that D1 receptors form the hetero-oligomer with D2 receptors, and that the D1–D2 receptor hetero-oligomer preferentially couples to Gq/PLC signaling (Rashid et al., 2007a,b). The expression of dopamine D1 and D2 receptors are largely segregated in direct and indirect pathway neurons in the dorsal striatum, respectively (Gerfen et al., 1990; Hersch et al., 1995; Heiman et al., 2008). However, some proportion of medium spiny neurons are known to expresses both D1 and D2 receptors (Hersch et al., 1995). Gene expression analysis using single cell RT-PCR technique estimated that 40% of medium spiny neurons express both D1 and D2 receptor mRNA (Surmeier et al., 1996).
  4. ↑ Ferré S, Bonaventura J, Tomasi D, Navarro G, Moreno E, Cortés A, Lluís C, Casadó V, Volkow ND (June 2015). "Allosteric mechanisms within the adenosine A2A-dopamine D2 receptor heterotetramer". Neuropharmacology. 104: 154–60. doi:10.1016/j.neuropharm.2015.05.028. PMC   5754196 . PMID   26051403. caffeine-induced increases in D2R availability in the ventral striatum were associated with caffeine-induced increases in alertness (Volkow et al., 2015). ... Fig. 2. Brain maps showing significant differences in D2R/D3R availability (nondisplaceable binding potential or BPND), between placebo and caffeine
  5. ↑ Benarroch EE (July 2012). "Effects of acetylcholine in the striatum. Recent insights and therapeutic implications". Neurology. 79 (3): 274–81. doi:10.1212/WNL.0b013e31825fe154. PMID   22802594. S2CID   29003596.
  6. ↑ Gardoni F, Bellone C (2015). "Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction diseases". Frontiers in Cellular Neuroscience. 9: 25. doi: 10.3389/fncel.2015.00025 . PMC   4345909 . PMID   25784855. In particular in the striatum the release of DA rapidly influences synaptic transmission modulating both AMPA and NMDA receptors.
  7. ↑ Reinius B, Blunder M, Brett FM, Eriksson A, Patra K, Jonsson J, Jazin E, Kullander K (27 March 2015). "Conditional targeting of medium spiny neurons in the striatal matrix". Frontiers in Behavioral Neuroscience. 9: 71. doi: 10.3389/fnbeh.2015.00071 . PMC   4375991 . PMID   25870547.
  8. ↑ Kawaguchi Y, Wilson CJ, Emson PC (October 1990). "Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin". The Journal of Neuroscience. 10 (10): 3421–38. doi: 10.1523/JNEUROSCI.10-10-03421.1990 . PMC   6570194 . PMID   1698947.
  9. ↑ Tepper JM, Wilson CJ, Koós T (August 2008). "Feedforward and feedback inhibition in neostriatal GABAergic spiny neurons". Brain Research Reviews. 58 (2): 272–81. doi:10.1016/j.brainresrev.2007.10.008. PMC   2562631 . PMID   18054796.
  10. ↑ Ibáñez-Sandoval O, Tecuapetla F, Unal B, Shah F, Koós T, Tepper JM (May 2010). "Electrophysiological and morphological characteristics and synaptic connectivity of tyrosine hydroxylase-expressing neurons in adult mouse striatum". The Journal of Neuroscience. 30 (20): 6999–7016. doi:10.1523/JNEUROSCI.5996-09.2010. PMC   4447206 . PMID   20484642.
  11. ↑ Tepper JM, Tecuapetla F, Koós T, Ibáñez-Sandoval O (December 2010). "Heterogeneity and diversity of striatal GABAergic interneurons". Frontiers in Neuroanatomy. 4: 150. doi: 10.3389/fnana.2010.00150 . PMC   3016690 . PMID   21228905.
  12. ↑ English DF, Ibanez-Sandoval O, Stark E, Tecuapetla F, Buzsáki G, Deisseroth K, Tepper JM, Koos T (December 2011). "GABAergic circuits mediate the reinforcement-related signals of striatal cholinergic interneurons". Nature Neuroscience. 15 (1): 123–30. doi:10.1038/nn.2984. PMC   3245803 . PMID   22158514.
  13. ↑ Ibáñez-Sandoval O, Tecuapetla F, Unal B, Shah F, Koós T, Tepper JM (November 2011). "A novel functionally distinct subtype of striatal neuropeptide Y interneuron". The Journal of Neuroscience. 31 (46): 16757–69. doi:10.1523/JNEUROSCI.2628-11.2011. PMC   3236391 . PMID   22090502.
  14. ↑ Hikosaka O, Takikawa Y, Kawagoe R (July 2000). "Role of the basal ganglia in the control of purposive saccadic eye movements". Physiological Reviews. 80 (3): 953–78. doi:10.1152/physrev.2000.80.3.953. PMID   10893428.
  15. 1 2 Lanciego JL, Luquin N, Obeso JA (December 2012). "Functional neuroanatomy of the basal ganglia". Cold Spring Harbor Perspectives in Medicine. 2 (12): a009621. doi:10.1101/cshperspect.a009621. PMC   3543080 . PMID   23071379.
  16. 1 2 Freeze BS, Kravitz AV, Hammack N, Berke JD, Kreitzer AC (November 2013). "Control of basal ganglia output by direct and indirect pathway projection neurons". The Journal of Neuroscience. 33 (47): 18531–9. doi:10.1523/JNEUROSCI.1278-13.2013. PMC   3834057 . PMID   24259575.
  17. ↑ Albin RL, Young AB, Penney JB (October 1989). "The functional anatomy of basal ganglia disorders" (PDF). Trends in Neurosciences. 12 (10): 366–75. doi:10.1016/0166-2236(89)90074-x. hdl: 2027.42/28186 . PMID   2479133. S2CID   8112392.
  18. ↑ DeLong MR (July 1990). "Primate models of movement disorders of basal ganglia origin". Trends in Neurosciences. 13 (7): 281–5. doi:10.1016/0166-2236(90)90110-v. PMID   1695404. S2CID   4057704.
  19. ↑ Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC (July 2010). "Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry". Nature. 466 (7306): 622–6. Bibcode:2010Natur.466..622K. doi:10.1038/nature09159. PMC   3552484 . PMID   20613723.
  20. ↑ Bezard E, Jaber M, Gonon F, Boireau A, Bloch B, Gross CE (August 2000). "Adaptive changes in the nigrostriatal pathway in response to increased 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration in the mouse". The European Journal of Neuroscience. 12 (8): 2892–900. doi:10.1046/j.1460-9568.2000.00180.x. PMID   10971632. S2CID   8984006.
  21. ↑ Roze E, Bonnet C, Betuing S, Caboche J (2010). "Huntington's disease". Advances in Experimental Medicine and Biology. 685: 45–63. doi:10.1007/978-1-4419-6448-9_5. ISBN   978-1-4419-6447-2. PMID   20687494.
  22. ↑ Schroll H, Hamker FH (December 2013). "Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy". Frontiers in Systems Neuroscience. 7: 122. doi: 10.3389/fnsys.2013.00122 . PMC   3874581 . PMID   24416002.
  23. ↑ Klaus A, Martins GJ, Paixao VB, Zhou P, Paninski L, Costa RM (August 2017). "The Spatiotemporal Organization of the Striatum Encodes Action Space". Neuron. 95 (5): 1171–1180.e7. doi:10.1016/j.neuron.2017.08.015. PMC   5584673 . PMID   28858619.
  24. ↑ Cui G, Jun SB, Jin X, Pham MD, Vogel SS, Lovinger DM, Costa RM (February 2013). "Concurrent activation of striatal direct and indirect pathways during action initiation". Nature. 494 (7436): 238–42. Bibcode:2013Natur.494..238C. doi:10.1038/nature11846. PMC   4039389 . PMID   23354054.
  25. ↑ Markowitz JE, Gillis WF, Beron CC, Neufeld SQ, Robertson K, Bhagat ND, Peterson RE, Peterson E, Hyun M, Linderman SW, Sabatini BL, Datta SR (June 2018). "The Striatum Organizes 3D Behavior via Moment-to-Moment Action Selection". Cell. 174 (1): 44–58.e17. doi:10.1016/j.cell.2018.04.019. PMC   6026065 . PMID   29779950.
  26. ↑ Nambu A (December 2008). "Seven problems on the basal ganglia". Current Opinion in Neurobiology. 18 (6): 595–604. doi:10.1016/j.conb.2008.11.001. PMID   19081243. S2CID   24956799.
  27. ↑ Calabresi P, Picconi B, Tozzi A, Ghiglieri V, Di Filippo M (August 2014). "Direct and indirect pathways of basal ganglia: a critical reappraisal". Nature Neuroscience. 17 (8): 1022–30. doi:10.1038/nn.3743. PMID   25065439. S2CID   8983260.
  28. ↑ Tecuapetla F, Jin X, Lima SQ, Costa RM (July 2016). "Complementary Contributions of Striatal Projection Pathways to Action Initiation and Execution". Cell. 166 (3): 703–715. doi: 10.1016/j.cell.2016.06.032 . PMID   27453468.
  29. ↑ Jin X, Tecuapetla F, Costa RM (March 2014). "Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences". Nature Neuroscience. 17 (3): 423–30. doi:10.1038/nn.3632. PMC   3955116 . PMID   24464039.
  30. ↑ Geddes CE, Li H, Jin X (June 2018). "Optogenetic Editing Reveals the Hierarchical Organization of Learned Action Sequences". Cell. 174 (1): 32–43.e15. doi:10.1016/j.cell.2018.06.012. PMC   6056013 . PMID   29958111.
  31. ↑ Atallah HE, McCool AD, Howe MW, Graybiel AM (June 2014). "Neurons in the ventral striatum exhibit cell-type-specific representations of outcome during learning". Neuron. 82 (5): 1145–56. doi:10.1016/j.neuron.2014.04.021. PMC   4108162 . PMID   24908491.
  32. ↑ Kravitz AV, Tye LD, Kreitzer AC (June 2012). "Distinct roles for direct and indirect pathway striatal neurons in reinforcement". Nature Neuroscience. 15 (6): 816–8. doi:10.1038/nn.3100. PMC   3410042 . PMID   22544310.
  33. ↑ Vicente AM, Galvão-Ferreira P, Tecuapetla F, Costa RM (April 2016). "Direct and indirect dorsolateral striatum pathways reinforce different action strategies". Current Biology. 26 (7): R267-9. doi:10.1016/j.cub.2016.02.036. PMC   4826435 . PMID   27046807.
  34. 1 2 Baliki MN, Mansour A, Baria AT, Huang L, Berger SE, Fields HL, Apkarian AV (October 2013). "Parceling human accumbens into putative core and shell dissociates encoding of values for reward and pain". The Journal of Neuroscience. 33 (41): 16383–93. doi:10.1523/JNEUROSCI.1731-13.2013. PMC   3792469 . PMID   24107968. Recent evidence indicates that inactivation of D2 receptors, in the indirect striatopallidal pathway in rodents, is necessary for both acquisition and expression of aversive behavior, and direct pathway D1 receptor activation controls reward-based learning (Hikida et al., 2010; Hikida et al., 2013). It seems we can conclude that direct and indirect pathways of the NAc, via D1 and D2 receptors, subserve distinct anticipation and valuation roles in the shell and core of NAc, which is consistent with observations regarding spatial segregation and diversity of responses of midbrain dopaminergic neurons for rewarding and aversive conditions, some encoding motivational value, others motivational salience, each connected with distinct brain networks and having distinct roles in motivational control (Bromberg-Martin et al., 2010; Cohen et al., 2012; Lammel et al., 2013). ... Thus, the previous results, coupled with the current observations, imply that the NAc pshell response reflects a prediction/anticipation or salience signal, and the NAc pcore response is a valuation response (reward predictive signal) that signals the negative reinforcement value of cessation of pain (i.e., anticipated analgesia).

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.