Aproximación al Prototipo

4.2.1 Oculomotor Nucleus

This nucleus expresses estrogen receptors, 5α reductase, aromatase, and corticotropin

releasing hormone (57, 93, 95). It receives projections from the dorsolateral vestibular nucleus (284).

4.2.2 Red Nucleus

The red nucleus is the main premotor nucleus involved in limb movement, and is very poorly developed in snakes (285). The magnocellular neurons of this nucleus express

207). The strongest projections to the red nucleus come from the ipsilateral pretectal genicular nucleus and bilateral ventrolateral geniculate nuclei (216). Additional projections come from the ipsilateral ventromedial thalamic nucleus, ventrolateral thalamic nucleus, entopeduncular nucleus, suparpenduncular nucleus, dorsolateral hypothalamic nucleus, lateral hypothalamic area supramammillary nucleus, nucleus of the posterior commissure, lentiform thalamic nucleus, torus semicircularis, profound mesencephalic nucleus, reticular formation, and descending vestibular nucleus (167). In addition, the red nucleus receives contralateral projections from the lateral cerebellar nucleus (285).

4.2.3 Substantia Nigra

The substantia nigra is one of the two main dopamine producing nuclei of the brain, except in snakes were there does not seem to be a division between the dopaminergic nuclei (286). It consists of the two parts: a reticulated, cell-poor part and a compact, cell-dense part (37). In addition to dopamine, neurons express neuropeptide-Y and nitric oxide (37). The substantia nigra projects to the optic tectum, posterior medial nucleus, red nucleus, accumbens nucleus and septum and has reciprocal connections with the dorsal striatum (52, 113, 134). It receives input expressing dopamine receptors, cholecystokinin, neuropeptide-Y, orexin, nitric oxide, neuropeptide-FF and thyrotropin releasing hormone (37, 53, 54, 125, 138)

Activity in this region increases during copulation (164). In subordinate males, but not dominant males, serotonergic activity decreases during an aggressive interaction (114). Viewing dominant colouration or aggressive display behaviours increases dopaminergic, serotonergic and noradrenergic activity (111, 287). After an aggressive interaction, dopaminergic activity increases in the dominant male (72). The density of dopaminergic cells increases with the frequency of male courtship displays (183). The number of dopaminergic cells also increases in late vitellogenic females compared to previtellogenic females (193).

4.2.4 Ventral Tegmental Area

The ventral tegmental area is one of two primary dopaminergic brain nuclei (286). It also expresses progesterone receptors, nitric oxide, and calcitonin gene-related peptide

(91, 108). The ventral striatum has reciprocal connections with the ventral tegmental area (113). Bilateral input comes from the habenula and it receives additional input from the septum and accumbens nucleus (180, 195, 207). Innervating fibres express dopamine receptors, nitric oxide, cholecystokinin, thyrotropin releasing hormone, neuropeptide-FF and orexin (53, 54, 96, 125, 138). It sends projections to the septum, anterior dorsal ventricular ridge, diagonal band of Broca, olfactory tubercle, accumbens nucleus, olfactostriatum, dorsomedial & dorsolateral thalamic nuclei, dorsal hypothalamic area, ventromedial hypothalamic nucleus, lateral hypothalamic area, (52). Activity in this region increases during an aggressive interaction and during courtship (164). When faced with an unfamiliar opponent, dominant males show an increase in norepinephrine in the ventral tegmental area (117). In contrast, when faced with a familiar opponent, dopamine, norepinephrine and epinephrine increase in the subordinate male (111, 117). Dopamine, norepinephrine & serotonin activity also increase when viewing a dominant opponent (287). During an aggressive encounter, there is decreased serotonergic activity in the subordinate male (114). After an aggressive interaction, dopamine activity increases in the dominant individual (72). Stress increases serotonergic, dopaminergic, noradrenergic and adrenergic activity (116). Males from a ‘feminizing’ incubation temperature upregulate dopaminergic cell number in response to testosterone, while males from a ‘masculinizing’ temperature do not (198).

4.3 Isthmus

4.3.1 Central Grey

The central grey expresses tyrosine hydroxylase and the R1α regulatory kinase subunit

(41, 164). Projections come from the hypoglossal nucleus (166). It sends reciprocal connections to the septum and projects to the ventromedial hypothalamic nucleus (52, 128, 180). It is innervated by fibres expressing galanin, orexin, thyrotropin releasing hormone, and (sparsley) calcitonin gene-related peptide (54, 108, 125, 228).

4.3.2 Raphe Nuclei

The raphe consists of a superior nucleus and an inferior nucleus. It is the primary serotonin-producing region of the brain (216). Both nuclei also express progesterone

receptors, dopamine receptors, nitric oxide and 5α reductase (53, 91, 95). Serotonergic

neurons receive projections expressing orexin (54). Dopamine receptor expressing cells receive input from fibres expressing tyrosine hydroxylase (53). The superior raphe receives additional thyrotropin-releasing hormone projections (125). The inferior raphe expresses androgen and estrogen receptors (56, 57, 90). Both nuclei receive projections from the septum and project to the olfactostriatum, septum and dorsal cortex (52, 180). While both nuclei project to the accumbens nucleus, only the the superior raphe receives reciprocal projections from the accumbens nucleus (195). The superior raphe also projects to the dorsomedial and dorsolateral thalamic nuclei, dorsal hypothalamic area, ventromedial hypothalamic nucleus, and lateral hypothalamic area (98, 128, 167). Serotonergic activity inhibits aggression, and activity in the inferior nucleus increases during aggressive interactions (110, 164). During an aggressive encounter between two males without an established dominance hierarchy, serotonergic and dopaminergic activity are both reduced (112). After an aggressive interaction, serotonergic activity in subordinate male decreases and it either decreases slightly or increases in the dominant male (114, 288). When a male views a subordinate opponent, serotonergic activity in the raphe decreases and noradrenergic activity increases (287). When a male views a dominant opponent, serotonergic and dopaminergic activity increase (287). Serotonin synthesis increases with long-term alcohol consumption, more in the right hemisphere than in the left (289). The right hemisphere is associated with aggressive behaviour in lizards, and this is reduced following chronic alcohol consumption (289). Stress increases serotonergic, dopaminergic, noradrenergic and adrenergic activity (71, 116). Exercise also increases serotonergic activity (104).

4.3.3 Locus Coeruleus

Neuronal cell bodies express progesterone receptors, noradrenaline and nitric oxide (91, 125). Orexin-, nitrix oxide-, neuropeptide-FF- and thyrotropin releasing hormone- expressing fibres innervate the locus coeruleus (54, 96, 125). This is the main noradrenergic brain nucleus, sending noradrenergic projections to rest of the brain,

including the dorsolateral thalamic nucleus, septum and accumbens nucleus (52, 98, 194).

When a male encounters a threatening, unfamiliar opponent, serotonergic activity in the locus coeruleus increases (117). During an aggressive interaction, serotonergic activity increases and dopaminergic activity decreases when observing a dominant male, whereas serotonergic activity decreases and noradrenergic activity increases when observing a subordinate male (114, 287). After an aggressive encounter, serotonergic and dopaminergic activity increase in both the subordinate and dominant males (72, 112, 114, 287). Serotonergic activity also increases in animals when they are under physical exertion (104). In response to restraint stress, for example by manually restraining a lizard, serotonergic, dopaminergic, noradrenergic and adrenergic activity all increase (71, 104, 116).

4.3.4 Trochlear Nucleus

This nucleus expresses estrogen receptors and 5α reductase (57, 95, 207).

4.3.5 Isthmal Nuclei

There are two isthmal nuclei: the superior isthmal nucleus is magnocellular and the inferior isthmal nucleus is parvocellular. Both nuclei express vitamin D3 receptors and receive projections expressing calcitonin gene-related peptide and neuropeptide-FF, and the parvocellular nucleus also receives cholecystokinin, tyrosine hydroxylase, and nitric oxide projections (48, 53, 96, 108, 138). The tyrosine hydroxylase expressing fibres surround dopamine receptor expressing cells (53). The superior isthmal nucleus projects to the ventromedial hypothalamic nucleus and the posterior medial nucleus of the thalamus, while the inferior isthmal nucleus projects to the dorsal hypothalamic area (128, 134, 167).

4.3.6 Interpeduncular Nucleus

This nucleus contains serotonin-expressing cell bodies (216). It receives projections from the septum, accumbens nucleus, medial habenula (180, 195). It receives projections expressing cholecystokinin, thyrotropin releasing hormone, calcitonin gene-

related peptide, mesotocin, corticotropin releasing hormone and gonadotropin releasing hormone (22, 93, 108, 125, 138). The neuropil expresses nitric oxide (127).

5 Hindbrain 5.1 Cerebellum

The cerebellum is the only region outside the telencephalon known to have constitutive neurogenesis in adults (29, 73). Though there is some indication the neurogenesis occurs in the habenula and third ventricle (204, 205). It consists of a dorsal cellular layer and a ventral plexiform layer and projects to the red nucleus (97, 216). Cells

express nitric oxide synthase, vitamin D3 receptors, progesterone receptors and the R1α

regulatory kinase subunit, and receive somatostatin, gonadotropin-releasing hormone and calcitonin gene-related peptide input (41, 45, 48, 91, 108, 239). There is some evidence for mosaic evolution of cerebellum volume (290).