A serotonin pathway identifies aggregate projections from neurons which synthesize and communicate the monoamine neurotransmitter serotonin.[ citation needed ] These pathways are relevant to different psychiatric and neurological disorders. [1] [2] [3]
| Pathway Group | Origin [4] | Projections | Notes |
|---|---|---|---|
| Rostral Group | Caudal linear nucleus (cell group B8) | Shares overlap with the dorsal raphe nuclei | |
| Dorsal raphe nucleus (cell groups B6, B7) | The anterior dorsal raphe primarily projects to the cortex, neostriatum, amygdala and SN, while the caudal division of the dorsal raphe projects to the latter three. The highest density of cortical innervation is in layer 1. | ||
| Median raphe nucleus (cell groups B5, B8) | Projections into the hippocampus are the most dense in the subiculum, followed by Ammon's horn and the Dentate gyrus. Projections into the VTA modulate firing rate, increasing the rate with lower activity, and depressing it with higher activity. | ||
| Caudal Group | Nucleus raphe magnus (cell group B3) | ||
| Nucleus raphe obscurus (cell group B2) |
| All three of the trigeminal motor nuclei receive dense innervations. | |
| Nucleus raphe pallidus (cell group B1) |
| Some of the serotonergic spinal cord axons may originate in the spinal cord itself. | |
| Lateral medullary reticular formation |
Given the wide area that the many serotonergic neurons innervate, these pathways are implicated in many functions, as listed above. The caudal serotonergic nuclei heavily innervate the spinal cord, medulla and cerebellum. In general, manipulation of the caudal nuclei(e.g. pharmacological, lesion, receptor knockout) that results in decreased activity decreases movement, while manipulations to increase activity cause an increase in motor activity. Serotonin is also implicated in sensory processing, as sensory stimulation causes an increase in extracellular serotonin in the neocortex. Serotonin pathways are thought to modulate eating, both the amount as well as the motor processes associated with eating. The serotonergic projections into the hypothalamus are thought to be particularly relevant, and an increase in serotonergic signaling is thought to generally decrease food consumption (evidenced by fenfluramine, however, receptor subtypes might make this more nuanced). Serotonin pathways projecting into the limbic forebrain are also involved in emotional processing, with decreased serotonergic activity resulting in decreased cognition and an emotional bias towards negative stimuli. [5] The function of serotonin in mood is more nuanced, with some evidence pointing towards increased levels leading to depression, fatigue and sickness behavior; and other evidence arguing the opposite. [6]
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction. Approximately 90% of the serotonin that the body produces is in the intestinal tract.
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the release of serotonin. The anxiolytic drug Buspirone acts as partial agonist against these receptors. Selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to act in these nuclei, as well as at their targets.
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.
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.
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.
The caridoid escape reaction, also known as lobstering or tail-flipping, refers to an innate escape mechanism in marine and freshwater crustaceans such as lobsters, krill, shrimp and crayfish.
The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formation make up a complex set of networks in the core of the brainstem that extend from the upper part of the midbrain to the lower part of the medulla oblongata. The reticular formation includes ascending pathways to the cortex in the ascending reticular activating system (ARAS) and descending pathways to the spinal cord via the reticulospinal tracts.
Neuropharmacology is the study of how drugs affect function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain. Molecular neuropharmacology involves the study of neurons and their neurochemical interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central and peripheral nervous systems. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, psychological disorders, addiction, and many others.
In neuroanatomy, thalamocortical radiations are the fibers between the thalamus and the cerebral cortex.
The orbitofrontal cortex (OFC) is a prefrontal cortex region in the frontal lobes of the brain which is involved in the cognitive process of decision-making. In non-human primates it consists of the association cortex areas Brodmann area 11, 12 and 13; in humans it consists of Brodmann area 10, 11 and 47.
The dorsal raphe nucleus is located on the midline of the brainstem and is one of the raphe nuclei. It has rostral and caudal subdivisions.
The median raphe nucleus, also known as the nucleus raphes medianus (NRM) or superior central nucleus, is a brain region composed of polygonal, fusiform, and piriform neurons, which exists rostral to the nucleus raphes pontis. The MRN is located between the posterior end of the superior cerebellar peduncles and the V. Afferents of the motor nucleus. It is one of two nuclei, the other being the dorsal raphe nucleus (DnR), in the midbrain-pons.
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.
The pre-Bötzinger complex (preBötC) is a cluster of interneurons in the ventral respiratory group of the medulla of the brainstem. This complex has been proven to be essential for the generation of the respiratory rhythm in mammals. The exact mechanism of the rhythm generation and transmission to motor nuclei remains controversial and the topic of much research.
The median preoptic nucleus is located dorsal to the other three nuclei of the preoptic area of the anterior hypothalamus. The hypothalamus is located just beneath the thalamus, the main sensory relay station of the nervous system, and is considered part of the limbic system, which also includes structures such as the hippocampus and the amygdala. The hypothalamus is highly involved in maintaining homeostasis of the body, and the median preoptic nucleus is no exception, contributing to regulation of blood composition, body temperature, and non-REM sleep.
Scientific studies have found that different brain areas show altered activity in humans with major depressive disorder (MDD), and this has encouraged advocates of various theories that seek to identify a biochemical origin of the disease, as opposed to theories that emphasize psychological or situational causes. Factors spanning these causative groups include nutritional deficiencies in magnesium, vitamin D, and tryptophan with situational origin but biological impact. Several theories concerning the biologically based cause of depression have been suggested over the years, including theories revolving around monoamine neurotransmitters, neuroplasticity, neurogenesis, inflammation and the circadian rhythm. Physical illnesses, including hypothyroidism and mitochondrial disease, can also trigger depressive symptoms.
Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transmits into non-rapid eye movement sleep but under certain circumstances it is possible to transit from wakefulness directly into rapid eye movement sleep.
A spinal interneuron, found in the spinal cord, relays signals between (afferent) sensory neurons, and (efferent) motor neurons. Different classes of spinal interneurons are involved in the process of sensory-motor integration. Most interneurons are found in the grey column, a region of grey matter in the spinal cord.
Epigenetics of depression is the study of how epigenetics contribute to depression.
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