Editing Substantia nigra (section)

== Function ==
The substantia nigra is an important player in brain function, in particular, in [[eye movement (sensory)|eye movement]], [[motor planning]], [[reward system|reward-seeking]], [[learning]], and [[addiction]]. Many of the substantia nigra's effects are mediated through the [[striatum]]. The nigral [[dopaminergic]] input to the striatum via the [[nigrostriatal pathway]] is intimately linked with the striatum's function.<ref name="striatum">{{cite journal | vauthors = Nicola SM, Surmeier J, Malenka RC | title = Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens | journal = Annual Review of Neuroscience | volume = 23 | pages = 185–215 | year = 2000 | pmid = 10845063 | doi = 10.1146/annurev.neuro.23.1.185 | author-link2 = D. James Surmeier }}</ref> The co-dependence between the striatum and substantia nigra can be seen in this way: when the substantia nigra is electrically stimulated, no movement occurs; however, the symptoms of nigral degeneration due to Parkinson's is a poignant example of the substantia nigra's influence on movement. In addition to striatum-mediated functions, the substantia nigra also serves as a major source of [[GABAergic]] inhibition to various brain targets.

===Pars reticulata===
{{main|Pars reticulata#Function}}
The [[pars reticulata]] of the substantia nigra is an important processing center in the basal ganglia. The GABAergic neurons in the pars reticulata convey the final processed signals of the [[basal ganglia]] to the [[thalamus]] and [[superior colliculus]]. In addition, the pars reticulata also inhibits dopaminergic activity in the [[pars compacta]] via axon collaterals, although the functional organization of these connections remains unclear.

The GABAergic neurons of the pars reticulata spontaneously fire [[action potential]]s. In rats, the frequency of action potentials is roughly 25&nbsp;Hz.<ref>{{cite journal | vauthors = Gernert M, Fedrowitz M, Wlaz P, Löscher W | title = Subregional changes in discharge rate, pattern, and drug sensitivity of putative GABAergic nigral neurons in the kindling model of epilepsy | journal = The European Journal of Neuroscience | volume = 20 | issue = 9 | pages = 2377–86 | date = November 2004 | pmid = 15525279 | doi = 10.1111/j.1460-9568.2004.03699.x | s2cid = 24485657 | doi-access = free }}</ref> The purpose of these spontaneous action potentials is to inhibit targets of the basal ganglia, and decreases in inhibition are associated with movement.<ref>{{cite journal | vauthors = Sato M, Hikosaka O | title = Role of primate substantia nigra pars reticulata in reward-oriented saccadic eye movement | journal = The Journal of Neuroscience | volume = 22 | issue = 6 | pages = 2363–73 | date = March 2002 | pmid = 11896175 | pmc = 6758246 | doi = 10.1523/JNEUROSCI.22-06-02363.2002 }}</ref> The subthalamic nucleus gives excitatory input that modulates the rate of firing of these spontaneous action potentials. However, lesion of the subthalamic nucleus leads to only a 20% decrease in pars reticulata firing rate, suggesting that the generation of action potentials in the pars reticulata is largely autonomous,<ref>{{cite journal | vauthors = Zahr NM, Martin LP, Waszczak BL | title = Subthalamic nucleus lesions alter basal and dopamine agonist stimulated electrophysiological output from the rat basal ganglia | journal = Synapse | volume = 54 | issue = 2 | pages = 119–28 | date = November 2004 | pmid = 15352137 | doi = 10.1002/syn.20064 | s2cid = 10239473 }}</ref> as exemplified by the pars reticulata's role in [[saccade|saccadic eye movement]]. A group of GABAergic neurons from the pars reticulata projects to the superior colliculus, exhibiting a high level of sustained inhibitory activity.<ref>{{cite journal | vauthors = Hikosaka O, Wurtz RH | title = Visual and oculomotor functions of monkey substantia nigra pars reticulata. III. Memory-contingent visual and saccade responses | journal = Journal of Neurophysiology | volume = 49 | issue = 5 | pages = 1268–84 | date = May 1983 | pmid = 6864250 | doi = 10.1152/jn.1983.49.5.1268 }}</ref> Projections from the [[caudate nucleus]] to the superior colliculus also modulate saccadic eye movement.
Altered patterns of pars reticulata firing such as single-spike or burst firing are found in [[Parkinson's disease]]<ref>{{cite journal | vauthors = Tseng KY, Riquelme LA, Belforte JE, Pazo JH, Murer MG | title = Substantia nigra pars reticulata units in 6-hydroxydopamine-lesioned rats: responses to striatal D2 dopamine receptor stimulation and subthalamic lesions | journal = The European Journal of Neuroscience | volume = 12 | issue = 1 | pages = 247–56 | date = January 2000 | pmid = 10651879 | doi = 10.1046/j.1460-9568.2000.00910.x | s2cid = 22886675 | hdl = 11336/39220 | hdl-access = free }}</ref> and [[epilepsy]].<ref>{{cite journal | vauthors = Deransart C, Hellwig B, Heupel-Reuter M, Léger JF, Heck D, Lücking CH | title = Single-unit analysis of substantia nigra pars reticulata neurons in freely behaving rats with genetic absence epilepsy | journal = Epilepsia | volume = 44 | issue = 12 | pages = 1513–20 | date = December 2003 | pmid = 14636321 | doi = 10.1111/j.0013-9580.2003.26603.x | s2cid = 6661257 }}</ref>

===Pars compacta===
{{main|Pars compacta#Function}}
The most prominent function of the pars compacta is [[motor control]],<ref>{{cite journal | vauthors = Hodge GK, Butcher LL | title = Pars compacta of the substantia nigra modulates motor activity but is not involved importantly in regulating food and water intake | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 313 | issue = 1 | pages = 51–67 | date = August 1980 | pmid = 7207636 | doi = 10.1007/BF00505805 | s2cid = 24642979 }}</ref> though the substantia nigra's role in motor control is indirect; electrical stimulation of the substantia nigra does not result in movement, due to mediation of the striatum in the nigral influence of movement. The pars compacta sends excitatory input to the striatum via D1 pathway that excites and activates the striatum, resulting in the release of GABA onto the globus pallidus to inhibit its inhibitory effects on the thalamic nucleus. This causes the thalamocortical pathways to become excited and transmits motor neuron signals to the cerebral cortex to allow the initiation of movement, which is absent in Parkinson's disease. However, lack of pars compacta neurons has a large influence on movement, as evidenced by the symptoms of Parkinson's. The motor role of the pars compacta may involve fine motor control, as has been confirmed in animal models with lesions in that region.<ref>{{cite journal | vauthors = Pioli EY, Meissner W, Sohr R, Gross CE, Bezard E, Bioulac BH | title = Differential behavioral effects of partial bilateral lesions of ventral tegmental area or substantia nigra pars compacta in rats | journal = Neuroscience | volume = 153 | issue = 4 | pages = 1213–24 | date = June 2008 | pmid = 18455318 | doi = 10.1016/j.neuroscience.2008.01.084 | s2cid = 11239586 }}</ref>

The pars compacta is heavily involved in learned responses to stimuli. In primates, dopaminergic neuron activity increases in the nigrostriatal pathway when a new stimulus is presented.<ref name="conditioning">{{cite journal | vauthors = Ljungberg T, Apicella P, Schultz W | title = Responses of monkey dopamine neurons during learning of behavioral reactions | journal = Journal of Neurophysiology | volume = 67 | issue = 1 | pages = 145–63 | date = January 1992 | pmid = 1552316 | doi = 10.1152/jn.1992.67.1.145 | s2cid = 18024404 }}</ref> Dopaminergic activity decreases with repeated stimulus presentation.<ref name="conditioning" /> However, behaviorally significant stimulus presentation (i.e. rewards) continues to activate dopaminergic neurons in the substantia nigra pars compacta.  Dopaminergic projections from the [[ventral tegmental area]]  (bottom part of the "midbrain" or mesencephalon) to the prefrontal cortex (mesocortical pathway) and to the nucleus accumbens (mesolimbic pathway – "meso" referring to "from the mesencephalon"... specifically the [[ventral tegmental area]]) are implicated in reward, pleasure, and addictive behavior.  The pars compacta is also important in spatial learning, the observations about one's environment and location in space. Lesions in the pars compacta lead to learning deficits in repeating identical movements,<ref>{{cite journal | vauthors = Da Cunha C, Silva MH, Wietzikoski S, Wietzikoski EC, Ferro MM, Kouzmine I, Canteras NS | title = Place learning strategy of substantia nigra pars compacta-lesioned rats | journal = Behavioral Neuroscience | volume = 120 | issue = 6 | pages = 1279–84 | date = December 2006 | pmid = 17201473 | doi = 10.1037/0735-7044.120.6.1279 }}</ref> and some studies point to its involvement in a dorsal striatal-dependent, response-based memory system that functions relatively independent of the [[hippocampus]], which is traditionally believed to subserve spatial or [[episodic-like memory]] functions.<ref>{{cite journal | vauthors = Da Cunha C, Wietzikoski S, Wietzikoski EC, Miyoshi E, Ferro MM, Anselmo-Franci JA, Canteras NS | title = Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system | journal = Neurobiology of Learning and Memory | volume = 79 | issue = 3 | pages = 236–42 | date = May 2003 | pmid = 12676522 | doi = 10.1016/S1074-7427(03)00008-X | s2cid = 12045200 }}</ref>

The pars compacta also plays a role in [[temporal processing]] and is activated during time reproduction. [[Lesion]]s in the pars compacta leads to temporal deficits.<ref>{{cite journal | vauthors = Matell MS, Meck WH | title = Neuropsychological mechanisms of interval timing behavior | journal = BioEssays | volume = 22 | issue = 1 | pages = 94–103 | date = January 2000 | pmid = 10649295 | doi = 10.1002/(SICI)1521-1878(200001)22:1<94::AID-BIES14>3.0.CO;2-E }}</ref> As of late, the pars compacta has been suspected of regulating the sleep-wake cycle,<ref>{{cite journal | vauthors = Lima MM, Andersen ML, Reksidler AB, Vital MA, Tufik S | title = The role of the substantia nigra pars compacta in regulating sleep patterns in rats | journal = PLOS ONE | volume = 2 | issue = 6 | pages = e513 | date = June 2007 | pmid = 17551593 | pmc = 1876809 | doi = 10.1371/journal.pone.0000513 | editor1-last = Brosnan | bibcode = 2007PLoSO...2..513L | editor1-first = Sarah | doi-access = free }} {{open access}}</ref> which is consistent with symptoms such as [[insomnia]] and [[REM sleep]] disturbances that are reported by patients with [[Parkinson's disease]]. Even so, partial dopamine deficits that do not affect motor control can lead to disturbances in the sleep-wake cycle, especially REM-like patterns of neural activity while awake, especially in the [[hippocampus]].<ref>{{cite journal | vauthors = Dzirasa K, Ribeiro S, Costa R, Santos LM, Lin SC, Grosmark A, Sotnikova TD, Gainetdinov RR, Caron MG, Nicolelis MA | title = Dopaminergic control of sleep-wake states | journal = The Journal of Neuroscience | volume = 26 | issue = 41 | pages = 10577–89 | date = October 2006 | pmid = 17035544 | pmc = 6674686 | doi = 10.1523/JNEUROSCI.1767-06.2006 }}</ref>