nucleus accumbens nucleus accumbens the nucleus accumbens (nac or nacc; also known as the accumbens nucleus, or formerly as the nucleus accumbens septi, latin for "nucleus adjacent to the septum") 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. nucleus accumbensapproximate location of the nucleus accumbens in the brainnucleus accumbens of the mouse braindetailspart ofmesolimbic pathwaybasal ganglia (ventral striatum)partsnucleus accumbens shellnucleus accumbens coreidentifierslatinnucleus accumbens septiacronym(s)nac or naccmeshd009714neuronames277neurolex idbirnlex_727ta98a14.1.09.440ta25558fma61889anatomical terms of neuroanatomy different nacc subregions (core vs shell) and neuron subpopulations within each region (d1-type vs d2-type medium spiny neurons) are responsible for different cognitive functions. as a whole, the nucleus accumbens has a significant role in the cognitive processing of motivation, aversion, reward (i.e., incentive salience, pleasure, and positive reinforcement), and reinforcement learning (e.g., pavlovian-instrumental transfer); hence, it has a significant role in addiction. in addition, part of the nucleus accumbens core is centrally involved in the induction of slow-wave sleep. the nucleus accumbens plays a lesser role in processing fear (a form of aversion), impulsivity, and the placebo effect. it is involved in the encoding of new motor programs as well. structure the nucleus accumbens is an aggregate of neurons which is described as having an outer shell and an inner core. input major glutamatergic inputs to the nucleus accumbens include the prefrontal cortex (particularly the prelimbic cortex and infralimbic cortex), basolateral amygdala, ventral hippocampus, thalamic nuclei (specifically the midline thalamic nuclei and intralaminar nuclei of the thalamus), and glutamatergic projections from the ventral tegmental area (vta). the nucleus accumbens receives dopaminergic inputs from the ventral tegmental area, which connect via the mesolimbic pathway. the nucleus accumbens is often described as one part of a cortico-basal ganglia-thalamo-cortical loop. dopaminergic inputs from the vta modulate the activity of gabaergic neurons within the nucleus accumbens. these neurons are activated directly or indirectly by euphoriant drugs (e.g., amphetamine, opiates, etc.) and by participating in rewarding experiences (e.g., sex, music, exercise, etc.). another major source of input comes from the ca1 and ventral subiculum of the hippocampus to the dorsomedial area of the nucleus accumbens. slight depolarizations of cells in the nucleus accumbens correlates with positivity of the neurons of the hippocampus, making them more excitable. the correlated cells of these excited states of the medium spiny neurons in the nucleus accumbens are shared equally between the subiculum and ca1. the subiculum neurons are found to hyperpolarize (increase negativity) while the ca1 neurons "ripple" (fire > 50 hz) in order to accomplish this priming. the nucleus accumbens is one of the few regions that receives a high density of histaminergic projections from the tuberomammillary nucleus (the sole source of histamine neurons in the brain). output the output neurons of the nucleus accumbens send axonal projections to the basal ganglia and the ventral analog of the globus pallidus, known as the ventral pallidum (vp). the vp, in turn, projects to the medial dorsal nucleus of the dorsal thalamus, which projects to the prefrontal cortex as well as back to the ventral and to dorsal striatum. other efferents from the nucleus accumbens include connections with the tail of the ventral tegmental area, substantia nigra, and the reticular formation of the pons. shell the nucleus accumbens shell (nacc shell) is a substructure of the nucleus accumbens. the shell and core together form the entire nucleus accumbens. location: the shell is the outer region of the nucleus accumbens, and – unlike the core – is considered to be part of the extended amygdala, located at its rostral pole. cell types: neurons in the nucleus accumbens are mostly medium spiny neurons (msns) containing mainly d1-type (i.e., drd1 and drd5) or d2-type (i.e., drd2, drd3, and drd4) dopamine receptors. a subpopulation of msns contain both d1-type and d2-type receptors, with approximately 40% of striatal msns expressing both drd1 and drd2 mrna. these mixed-type nacc msns with both d1-type and d2-type receptors are mostly confined to the nacc shell. the neurons in the shell, as compared to the core, have a lower density of dendritic spines, less terminal segments, and less branch segments than those in the core. the shell neurons project to the subcommissural part of the ventral pallidum as well as the ventral tegmental area and to extensive areas in the hypothalamus and extended amygdala. function: the shell of the nucleus accumbens is involved in the cognitive processing of reward, including subjective "liking" reactions to certain pleasurable stimuli, motivational salience, and positive reinforcement. that nacc shell has also been shown to mediate specific pavlovian-instrumental transfer, a phenomenon in which a classically conditioned stimulus modifies operant behavior. a "hedonic hotspot" or pleasure center which is responsible for the pleasurable or "liking" component of some intrinsic rewards is also located in a small compartment within the medial nacc shell. addictive drugs have a larger effect on dopamine release in the shell than in the core. core the nucleus accumbens core (nacc core) is the inner substructure of the nucleus accumbens. location: the nucleus accumbens core is part of the ventral striatum, located within the basal ganglia. cell types: the core of the nacc is made up mainly of medium spiny neurons containing mainly d1-type or d2-type dopamine receptors. the d1-type medium spiny neurons mediate reward-related cognitive processes, whereas the d2-type medium spiny neurons mediate aversion-related cognition. the neurons in the core, as compared to the neurons in the shell, have an increased density of dendritic spines, branch segments, and terminal segments. from the core, the neurons project to other sub-cortical areas such as the globus pallidus and the substantia nigra. gaba is one of the main neurotransmitters in the nacc, and gaba receptors are also abundant. function: the nucleus accumbens core is involved in the cognitive processing of motor function related to reward and reinforcement and the regulation of slow-wave sleep. specifically, the core encodes new motor programs which facilitate the acquisition of a given reward in the future. the indirect pathway (i.e., d2-type) neurons in the nacc core which co-express adenosine a2a receptors activation-dependently promote slow-wave sleep. the nacc core has also been shown to mediate general pavlovian-instrumental transfer, a phenomenon in which a classically conditioned stimulus modifies operant behavior. cell types approximately 95% of neurons in the nacc are gabaergic medium spiny neurons (msns) which primarily express either d1-type or d2-type receptors; about 1–2% of the remaining neuronal types are large aspiny cholinergic interneurons and another 1–2% are gabaergic interneurons. compared to the gabaergic msns in the shell, those in the core have an increased density of dendritic spines, branch segments, and terminal segments. from the core, the neurons project to other sub-cortical areas such as the globus pallidus and the substantia nigra. gaba is one of the main neurotransmitters in the nacc, and gaba receptors are also abundant. these neurons are also the main projection or output neurons of the nucleus accumbens. neurochemistry some of the neurotransmitters, neuromodulators, and hormones that signal through receptors within the nucleus accumbens include: dopamine: dopamine is released into the nucleus accumbens following exposure to rewarding stimuli, including recreational drugs like substituted amphetamines, cocaine, nicotine and morphine. phenethylamine and tyramine: phenethylamine and tyramine are trace amines which are synthesized in neurons that express the aromatic amino acid hydroxylase (aadc) enzyme, which includes all dopaminergic neurons. both compounds function as dopaminergic neuromodulators which regulate the reuptake and release of dopamine into the nacc via interactions with vmat2 and taar1 in the axon terminal of mesolimbic dopamine neurons. glucocorticoids and dopamine: glucocorticoid receptors are the only corticosteroid receptors in the nucleus accumbens shell. l-dopa, steroids, and specifically glucocorticoids are currently known to be the only known endogenous compounds that can induce psychotic problems, so understanding the hormonal control over dopaminergic projections with regard to glucocorticoid receptors could lead to new treatments for psychotic symptoms. a recent study demonstrated that suppression of the glucocorticoid receptors led to a decrease in the release of dopamine, which may lead to future research involving anti-glucocorticoid drugs to potentially relieve psychotic symptoms. gaba: a recent study on rats that used gaba agonists and antagonists indicated that gabaa receptors in the nacc shell have inhibitory control on turning behavior influenced by dopamine, and gabab receptors have inhibitory control over turning behavior mediated by acetylcholine. glutamate: studies have shown that local blockade of glutamatergic nmda receptors in the nacc core impaired spatial learning. another study demonstrated that both nmda and ampa (both glutamate receptors) play important roles in regulating instrumental learning. serotonin (5-ht): overall, 5-ht synapses are more abundant and have a greater number of synaptic contacts in the nacc shell than in the core. they are also larger and thicker, and contain more large dense core vesicles than their counterparts in the core. function