Cross references: Amygdaloid Hippocampal Convergence NOTE: If you get an error message, click the error message. About 15 years ago, while I was volunteering with Food Not Bombs, one of my fellow volunteers was tricked into starting crack cocaine. As has happened to many others, she became instantly hooked. Since I wanted to help her, I switched my attention to drugs. It turned out that the part of our nervous systems most involved with addiction is the Nucleus Accumbens Septi (NAC), and I have been interested in the NAC ever since. I eventually found a successful treatment for drugs. You can read about it at: http://www.neurogenesis.com/ You might ask, "If the stuff works, why is it not more widely known?" Answer: Perhaps some of the huge profits generated by the illegal drug trade are used to keep the cure hidden. The Kolb & Whishaw book gives a very brief discussion of the NAC on [K&W: 438-441]. See: Historical Background & Free Book . Nucleus Accumbens Septi (Wiki) http://en.wikipedia.org/wiki/Nucleus_accumbens "The nucleus accumbens (NAc or NAcc), also known as the accumbens nucleus or 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.[1] The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum, which is part of the basal ganglia.[2] 
Medial surface, person facing to the left. Nucleus accumbens is very roughly in the area labeled 34. The nucleus accumbens has a significant role in the cognitive processing of motivation, pleasure, and reward and reinforcement learning, and hence has significant role in addiction.[3][4] It plays a lesser role in fear, impulsivity, and the placebo effect.[5][6][7] It is involved in the encoding of new motor programs as well.[3] Each cerebral hemisphere has its own nucleus accumbens. It is located where the head of the caudate and the anterior portion of the putamen meet just lateral to the septum pellucidum. The nucleus accumbens can be divided into two structures—the nucleus accumbens core and the nucleus accumbens shell. These structures have different morphology and function. Contents 1 Structure 1.1 Input 1.2 Output 1.3 Shell 1.4 Core 2 Cell types 3 Neurotransmitters 4 Function 4.1 Reward and reinforcement 4.2 Maternal behavior 5 Clinical significance 5.1 Addiction 5.2 Depression 5.3 Placebo effect 6 Additional images 7 References 8 External links My comment: Trust Wikipedia to cut through all the noise. I've been focused on the nucleus accumbens (NAC) for at least 15 years. I have several hundred pages of PubMed printouts and photocopies of textbooks about the NAC, yet this short article did a lot to bring my understanding of it into focus. The most important thing about this article is that it clearly declares that the output from the NAC is GABA ergic. That means that the axons which leave the NAC use GABA (gamma-aminobutyric acid ) as their neurotransmitter. This is fortunate for those of us trying to figure out how the brain works. Almost all Neurotransmitters have multiple Receptors, and the effect that a neurotransmitter has depends on with which of its various receptors it is interacting. Although many neurotransmitters can be either excitatory or inhibitory, depending on with which of their receptors they are interacting, all of GABA's receptors are inhibitory. Some are fast and some are slow, but all are inhibitory, and this simplifies our analysis considerably since there's never any question about the direction of the effect that the NAC is having on downstream neurons. It means that we can be confident that when the NAC receives excitatory input, it inhibits the neurons to which it transmits, and when the NAC receives inhibitory input, it disinhibits the neurons to which it transmits and that the disinhibited neurons then become more excited. James Olds, who discovered the NAC and spent much of his career studying it, dubbed it the 'Pleasure Center', and, indeed, the greater the level of the transmitter dopamine (DA) at the D2 receptors in the NAC, the greater the apparent pleasure experienced by the organism. I say "apparent" because much of the research has been done on mice, and their experience of pleasure is inferred from their behavior. However, the results with mice generalize completely to humans. For example, drugs such as heroin and cocaine both increase the level of DA at the D2 receptors in the NAC and also are reported by people who use them as being pleasurable. DA has both excitatory and inhibitory receptors. The D2 receptor is inhibitory (see: Dopamine Receptors ). That means that as the level of DA at the D2 receptors increases, the output neurons of the NAC are inhibited from transmitting GABA, their inhibitory neurotransmitter. This in turn disinhibits the neurons to which the NAC projects and allows them to become more excited. Notice that the NAC receives inputs from both the Amygdala (AMG) and the Hippocampus (HIP). This is important. The AMG is central to an organism's response to biological needs, including, but not limited to, sex and hunger. The HIP is central to memory. The convergence of input from the AMG and the HIP onto the NAC makes the NAC the part of the nervous system where current needs are juxtaposed with the memory of how those needs were satisfied in the past. Because our anthropocentric intellectual tradition makes many researchers reluctant to ascribe 'thinking' to nonhuman animals, when an experimental animal such as a mouse is seen to hesitate between two choices in a maze, starting to take first one path and then the other several times before deciding which way to go , it is said to be engaged in 'vicarious trial and error'. However, this 'vicarious trial and error' allows for a comparison between current needs, as sensed by the AMG, and memories of how such or similar needs were satisfied in the past, as recorded in the HIP. When the memory of past behavior matches the current need, the level of DA at the D2 receptors increases, the organism has a pleasurable sensation, the tonic inhibition of the neuroaxis by the NAC is released, and the organism behaves in a manner similar to what it remembers as having been a successful way of meeting the need in the past. Most of the above is from memory. I will search through my voluminous notes and try to provide specific references for the points made, but this will take time. comment on references: Reference [16] is a full length article: Neurochemistry of the Nucleus Accumbens and its Relevance to Depression and Antidepressant Action in Rodents http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475798/ "The NAc contains small populations of γ-aminobutylic acid (GABA)-containing and cholinergic interneurons, in addition to a large number of efferent GABAergic medium spiny projecting neurons [102]. The activity of projecting medium spiny neurons is regulated by glutamatergic afferents arising from the prefrontal cortex, hippocampus and amygdala, by dopaminergic afferents from the ventral tegmental area [124], by serotonergic afferents from the raphe nucleus, and by noradrenergic afferents from the locus ceruleus. A schematic diagram is shown in Fig.1. These afferents converge primarily on GABA neurons, the main output cells of this region [102]. In addition, GABAergic projection neurons receive inhibitory input, primarily from a small population of GABAergic and cholinergic interneurons [75] but also through feedfoward inhibition [125] and axon collaterals of neighboring medium spiny neurons [29]. Medium spiny neurons project to a restricted part of the globus pallidus and the substantia nigra from the core, whereas from the shell, they project not only to the subcommissural part of the ventral pallidum and the ventral tegmental area but also to widespread areas in the hypothalamus and extended amygdala [102]. NAc output is regulated by numerous systems including glutamatergic afferent from the medial prefrontal cortex and hippocampus, both of which differentially regulate activities in the shell and core subregions (Fig.2). Furthermore, various systems such as glutamate, dopamine, GABA, acetylcholine, serotonin and so on regulate each other through pre- and post- receptors (Fig.3). A schematic diagram about the relationships among typical receptors is shown in Fig.3. Recently, an emerging body of evidence suggests that the activities of medium spiny projecting neurons, as well as these afferents neurons, are regulated locally by several neuropeptides and transcriptional factors, which are expressed in the NAc, and which are up- or down-regulated by various stressful situations [110]." "It is well recognized that GABAergic neurons function as the main neurons in the NAc, and that the flow of information through the NAc is dependent on the activity of GABAergic spiny projecting neurons. " 58 Related citations: http://www.ncbi.nlm.nih.gov/pubmed?cmd=link&linkname=pubmed_pubmed&uid=18654637&log$=relatedarticles&logdbfrom=pmc 16 Cited by's: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475798/citedby/ References [17] and [18] were identical and blank when I first read this article. However they did have 167 Related citations which I reviewed in place of the missing reference texts: http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=7906426 After obtaining the list, I reordered it by Pub Date rather than Link Ranking. # 130 1984 Neurochemically specified subsystems in the basal ganglia. http://www.ncbi.nlm.nih.gov/pubmed/6149896 196 Related citations http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=6149896 6 Cited by's: http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_citedin&from_uid=6149896 #83 1993 Physiological and morphological properties of accumbens core and shell neurons recorded in vitro. http://www.ncbi.nlm.nih.gov/pubmed/8446922 172 Related citations http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=8446922 26 Cited by's: http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_citedin&from_uid=8446922 #68 1994 GABA synapses formed in vitro by local axon collaterals of nucleus accumbens neurons. http://www.ncbi.nlm.nih.gov/pubmed/8027793 "GABAergic medium-spiny neuron axons not only form the principal projections of the nucleus accumbens (nAcc) ..." "In culture, as in the intact nAcc, medium-spiny neurons account for over 95% of the cells and are GABAergic." 137 Related citations http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=8027793 7 Cited by's http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_citedin&from_uid=8027793 Free full text (PDF) http://www.jneurosci.org/content/14/7/4548.long
The Pleasure Centers (BTB) Beginner-Neurological Level http://thebrain.mcgill.ca/flash/d/d_03/d_03_cr/d_03_cr_que/d_03_cr_que.html "For a species to survive, its members must carry out such vital functions as eating, reproducing, and responding to aggression. Evolution has therefore developed certain areas in our brain whose role is to provide a pleasurable sensation as a “reward” for carrying out these vital functions. These areas are interconnected with one another to form what is known as the “reward circuit”. The ventral tegmental area (VTA), a group of neurons at the very centre of the brain, plays an especially important role in this circuit. The VTA receives information from several other regions that tell it how well various fundamental needs, and more specifically human needs, are being satisfied. The VTA then forwards this information to another structure further forward in the brain: the nucleus accumbens (NAC). To send this information to the nucleus accumbens the VTA uses a particular chemical messenger: dopamine (DA). The increase in the level of dopamine in the nucleus accumbens, and in other brain regions, reinforces the behaviours by which we satisfy our fundamental needs. " My comments: 1. Although this doesn't mention the receptors, it is consistent with the interpretation given above that increased DA at the D2 receptors relaxes the tonic inhibition exerted by the NACs GABA ergic output and thus facilitates behavior. 2. This is only the Beginner-Neurological Level . Click on the link. On the left side of the page there are links for Intermediate and Advanced, and on the right side of the page there are links for Social, Psychological, Cellular and Molecular. Each link leads to a different page covering the same topic from a different perspective. The next two references were links from this page.
http://thebrain.mcgill.ca/flash/d/d_03/d_03_cl/d_03_cl_que/d_03_cl_que.html
1983 21<22 & 22<23 * * Free full text Neural projections from nucleus accumbens to globus pallidus, substantia innominata, and lateral preoptic-lateral hypothalamic area http://www.ncbi.nlm.nih.gov/pubmed/6822855 "Abstract The anatomical organization and electrophysiological characteristics of a projection from the nucleus accumbens to anteroventral parts of the globus pallidus and to a subpallidal region that includes the substantia innominata (SI), the lateral preoptic area (LPO), and anterior parts of the lateral hypothalamic area (LHA) were investigated in the rat. Autoradiographic experiments, with injections of 3H-proline into different sites in the nucleus accumbens and adjacent caudoputamen, indicate that the descending fibers are organized topographically along both mediolateral and dorsoventral gradients, although labeled fibers from adjacent regions of the nucleus accumbens overlap considerably in the ventral globus pallidus and subpallidal region. Injections confined to the caudoputaman only labeled fibers in the globus pallidus. Retrograde transport experiments with the marker true blue confirmed that only the nucleus accumbens projects to the subpallidal region and that the caudoputamen projects upon the glubus pallidus in a topographically organized manner. In electrophysiological recording experiments single pulse stimulation (0.1 to 0.7 mA; 0.15 msec duration) of the nucleus accumbens changed the discharge rate of single neurons in the ventral globus pallidus and in the SI, LPO, and LHA. Typically, the responses were inhibition of neuronal discharge with latencies of 6 to 18 msec. Single pulse stimulation of the dorsolateral caudoputamen altered the discharge rate of single neurons in dorsal regions of the globus pallidus, with inhibition being the most frequently observed response. The results of these anatomical and electrophysiological experiments are complementary and indicate that fibers from the nucleus accumbens innervate the anteroventral region of the globus pallidus as well as the subpallidal region, while most fibers of the caudoputamen innervate the globus pallidus but not the subpallidal region. It appears, therefore, that these two components of the striatum have different output connections. The possible functional significance of these findings is discussed in relation to the projections of the subpallidal region, which may include an output to the mesencephalic locomotor region, and in relation to the nucleus accumbens afferents from the amygdala and hippocampal formation. 442 Similar articles: http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=6822855 29 Cited by's:
http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_citedin&from_uid=6822855 Free full text http://www.jneurosci.org/content/3/1/189.long 2002 Hippocampal and prefrontal cortical inputs monosynaptically converge with individual projection neurons of the nucleus accumbens. 2003 Individual nucleus accumbens-projection neurons receive both basolateral amygdala and ventral subicular afferents in rats. See: Amygdaloid Hippocampal Convergence . 2009 14<131 Cholinergic innervation and thalamic input in rat nucleus accumbens. 2012 6<131 Free Article Glutamate inputs to the nucleus accumbens: does source matter? 2015 The Nucleus Accumbens: A Comprehensive Review - FullText https://www.karger.com/Article/FullText/368279 Schematic representation of major afferent (a) and efferent (b) connections of the NAc. SNc = Substantia nigra pars compacta; BNST = bed nucleus of the stria terminalis; GPi = globus pallidus internus; SNr = substantia nigra pars reticulata; ctx = cortex. Nucleus Accumbens Septi 160226 - 1236 Aug 13, 2019 Aug 15, 2019 |
These
active approach and avoidance behaviours are under the control of what is sometimes
called the behavioural approach system (BAS). This system comprises
two main neural circuits: one corresponding to rewarded action and the other to
successful avoidance. 
Each hemisphere of the cerebrum is subdivided into four lobes visible from the outside:
The pleasurable (and addictive) effects of amphetamines, cocaine, and
perhaps other psychoactive drugs seem to depend on their producing
increasing levels of dopamine at the synapses in the nucleus accumbens (as well as the 
