Kisspeptin

• excreted by neurons in hypothalamus
• have excitatory effect on GNRH neurons 
• the neurons that release these become more active at puberty 

Male Female Difference 

Hypothalamus

• anterior paraventricular nuc is thought to control ovulatory cycles in women(GNRH release and affects prolactin release): not in males
• during development testosterone cause cell death in that region
• parts of preoptic areas in rostral hypothalamus are only in males (without testosterone they die in development)
• preoptic areas control many parts of sexual function

Hypothalamic control of lactation

• prolactin: development of milk secreting glandular tissue and production of milk; blocks GnRH release
• dopamine inhibits release of prolactin
• TRH and oxytocin effect prolactin release
• posterior pit releases oxytocin that contraction of myoepithelial cells for ejection of milk (requires lots of it helped by electrical coupling of oxytocin containing cells in pregnant women)

pathways connecting hypothalamus

to other brain regions

• posterior to brain stem is dorsal longitudinal fasciculus
• anterior is medial forebrain bundle
• hypothalamo-medullary and spinal pathways pass through Dorsal longitudinal fasciculus
• hypothalamo-medullary does cardiovascular and feeding

Hypothalamo-spinal pathway

• pass through dorsal longitudinal fasciculus and medulla
• located in lateral medula in btw the inferior olive and inferior cerebellar peduncle
• has sympathetic outflow
• cardiovascular function and sweating
• terminates in intermediate lateral horn and than go out into sypmathetic chain gangion 
• lesion in dorsal medulla supplied by PICA can cause horner syndrome 

Nucleus Accumbens

• plays significant role in motivation and rewarding behaviors
• shows increased activity when positive emotions are expressed
• nucleus accumbens and dopaminergic inputs have been implicated

Neocortical Structures of the

Lymbic System

• 6 layered cortex
• cingulate gyrus
• orbitofrontal and medial prefrontal cortex
• temporal pole
• subcallosal area

Paleocortex and Archicortex

• lymbic system
• paleocortex is 3-5 layers: entorhinal cortex
• archicortex is 3 layers: hipppocampal formation

subcortical forebrain structures

(lymbic system)

• amygdala
• septal nuclei
• ventral striatum (including nucleus accumbens)
• ventral pallidum (including substantial innominata, locus of the basal nucleus of meynert)

Diencephalic structures

(lymbic system)

• dorsal thalamus: anterior nucleus and medial dorsal nuc (dorsomedial nuc)
• habenula
• mammillary bodies

Papez circuit

• links hippocampus to several structures
• cingulate cortex recieves info from cerebral cortex and anterior nucleus
• projs via cingulum to entorhinal cortex
• entorhinal cortex also recieves input from widespreade areas of cortex(one part from olfactory bulb)
• projs to hippocampal formation to form association among multiple inputs through process of long term potentiation
• proj via fornix to mamillary body, this projects via mammilo-thalamic tract to anterior nuc of the thalamus
• this provides gateway by which processing reactes cingulate cortex, cortex provides an output to other areas of cerebral cortex that is a comparison of its inputs from both ant nuc of thalamus and from widespread neocortical areas

Functional roles of Papez circuitry

• consolidate short-term memory into long term memory
• forms relations among multiple elements of a memory: 
• memory in context, memory of facts and events
• spatial memory

Septal Nuclei

• located just ventral to septum pellucidum and rostral to anterior commisure
• input from hippocampal form via fornix, as well as from amygdala and ventral tegmental area of midbrain(dopaminergic)
• output to hippocampul form(via fornix) and to limbic assoc cortex, medial dorsal thalamic nuc and habenula via stria medullaris
• part of forebrain cholinergic system(includes cells in basal nuc of meynert)
• cholinergic inputs to hippocampus and neocortex are associated with arousal and synaptic plasticity
• alzheimers involves degeneration of cholinergic neurons in both of these nuclei

Korsakoff's Disease

• thiamine deficiency due to chronic alcoholism
• damages diencephalic structures (mamillary bodies and medial dorsal nuc of the thalamus)
• diminsh consolidation of short term memory to long term memory (Papez circuitry)

Alzheimer's Disease

• entorhinal cortex and hippocampal formation are involved at an early stage
• cholinergec cells of septal nuclei (and basal nucleus of meynert) are lost
• diminsh consolidation of short term memory to long term memory (Papez circuitry)
• degenerative?

Corticomedial nuclei

(amygdala)

• amygdala
• inputs: olfactory bulb
• outputs: (via stria terminalis) to ventromedial nuc of the hypothalamus
• function: mediates olfactory-based regulation of feeding behavior

Basolateral nuc

(amygdala)

Central Nucleus

(amygdala)

• inputs: basolateral amygdala(processed sens/emotional state) and viscerosensory input(solitary nuc)
• ouputs (amygdalofugal pathway): hypothalamus, brainstem centers, basal nuc of meynert(part of cholinergic forebrain)
• functions: mediates a variety of autonomic and behavioral responses to learned emotion stimuli
• functions: through basal nuc of meynert, proj to neocortex plays role in arousal and modification of responses in association of sensory cortex

three nuclei of the amygdala

• does emotions
• central nucleus
• basolateral nuclei
• cortocomedial nuclei

Substantia innominata

• GABAergic/cholinergic
• cortical activation, plasticity
• enhanced cortical response to conditioned stimuli

Ventral Tegemental area, 

locus ceruleus,

dorsal lateral tegmental area

• activation of modulatory pathways (dopamine, norepinephrine and acetycholine
• behavioral arousal, increased vigilance

Temporal Lobe lesion issues

• problems with:
• establishing emotional significance of sensory stimuli (fear, anger rage, sexual behavior)
• generate appropriate respones to emotion-laden sensory stimuli
• affective state

Urbach-Weithe Disease

• rare disorder that results in bilateral calcification of anterior-medial temporal lobes without damage to hippocampus or temporal neocortex
• cannot recognize emotional content in fearful facial expressions, while able to recognize positive emotional content of facial expressions
• does not experience fearful emotional reaction to many stimuli that normally evoke fear

Affective Disorders

• involve altered function of the amygdala
• implicated in PTSD: through a traumatic event, normally benign sensory stimuli become evoke strong negative emotional responses
• depression involves increased activation of the amygdala and associated regions including the orbitofrontal and medial prefrontal cortex and the mediodorsal nuc of the thalamus

Lobotomy

• emotional expression also depends on cingulate, orbitofrontal and medial prefrontal cortex, based in part on direct and inderect projections of amygdala
• basis of lobotomy: by severing inputs to prefrontal cortex, it was hoped that undesirable aspects of mood would be eliminated

Reward Centers of brain

• reinforced and regulated by a basal ganglia type circuit involving the ventral striatum(nuc accumbens), ventral pallidum and dopaminergic neurons of the ventral tegmental area
• ventral pallidum and striatum has reinforcing role in neocortical areas assoc with reward via mediodorsal nuc of the thalamus
• nuc accumbens is modulate dby dopaminergic input from the ventral tegmental area adjacent to the substantia nigra
• interconnections btw nuc accumb. and amygdala asses the emotional content and valence 
• habenula regulates activity of reward circ (actiavted by unpleasent events and inhibits dopaminergic ventral tegmental neurons)

Habenula

• posterior to the thalamus
• habenula neurons activated by unpleasant events
• inhibits dopaminergic ventral tegmental neurons that normally modulate nuc accumbens 

Addictive drugs and behaviors

• some subs act on dopaminergic ventral tegmental neurons to increase release onto nuc accumbens(aclohol, opiates, nicotine)
• some subs act in nuc accumbens to enhance dopamine release(opiates, cannabinoids, nicotine, cocaine, amphetamines)
• dopaminergic neurons of the VTA project to other centers of the limbic system(mesolimbic path) or to corticoareas(mesocorticolimbic path) to infliunece motivated behaviors