Limbic System - Learning, Memory, Emotion

Question 1

Thalamic relay neurons

Answer 1

Receive input from sensory systems and relay information via excitatory synapses in the cortex

Resting membrane potential hovers around -55mV and depolarization elicits a burst of high frequency action potentials

Inhibited by thalamic reticular neurons during slow wave sleep; resting potential is -85mV and depolarization elicits a 3Hz burst of APs with a Ca2+ spike

Question 2

What is the molecular mechanism of the delta wave?

Answer 2

T-type Ca2+ channels in thalamic relay neurons are normally inactivated by depolarization (-55mV resting potential); when the cell is hyperpolarized by thalamic reticular cells, the Ca2+ channels generate Ca2+ spikes at a frequency of 3Hz; this Ca2+ current triggers fast sodium potentials which excite cortical pyramidal cells at the same frequency

Question 3

How are T-Type Ca2+ channels related to seizures?

Answer 3

Mice with a mutation in T-Type Ca2+ channels which allow the thalamic relay neurons to fire slow Ca2+ spikes at depolarized resting potentials (-55mV) exhibit spontaneous absence seizures with slow waves in the EEG

Question 4

Ethosuximide and Valproic Acid

Answer 4

Anti-seizure medications which block T-type Ca2+ channels; effective in preventing absence epilepsy

Question 5

What is the role of ACh in the thalamocortical circuit?

Answer 5

ACh is released in the thalamus by stimulation of cholinergic neurons in the reticular activating system; ACh release in the thalamus results in awakening of an animal from sleep and interruption of slow waves in the EEG

Question 6

What is the role of NE in the thalamocortical circuit?

Answer 6

NE is released in the thalamus by stimulation of noradrenergic neurons in the locus coeruleus during the fight or flight response

Question 7

What is the role of serotonin in the thalamocortical circuit?

Answer 7

Serotonin is released in the thalamus by serotonergic neurons from the raphae nuclei

Question 8

Declarative memory

Answer 8

The ability to recollect events or facts that have a specific temporal and spatial context, as well as general knowledge about the world

Formation relies on the hippocampus; long term storage in the neocortex

Question 9

Procedural memory

Answer 9

The ability to learn new motor skills

Relies on the cerebellum, striatum, and frontal cortex

Question 10

Anterograde amnesia

Answer 10

The inability to form new memories of events that have taken place since the brain insult; memories formed before the insult are unaffected

Question 11

Short-term memory

Answer 11

Lasts on the order of seconds

Processing occurs in sensory cortex

Question 12

Working memory

Answer 12

Lasts on the order of seconds to minutes (i.e. cooking, finding lost keys)

Stored in the frontal lobes, near the centers for executive function

Significantly affected in frontotemporal dementia

Question 13

Long Term memory

Answer 13

Stored in the neocortex

Question 14

What is the circuitry of the hippocampus?

Answer 14

Receives input from the entorhinal cortex via the perforant path; these axons synapse on both the neurons of the dentate gyrus and the CA3 regions of Amon’s horn; CA3 also receives secondary input from the dentate gyrus via mossy fibers

CA3 projects to CA1 neurons via Schaeffer collaterals; CA3 and CA1 send output from the hippocampus through axons of the fornix

Cells in the dentate gyrus send mossy fibers to

Question 15

Associative memory

Answer 15

Learning to associate several cues with a particular fact or object; mediated by long term potentiation in the CA3 area of the hippocampus

Question 16

What is the mechanism of LTP?

Answer 16

Tetanic stimulation of the perforant path on CA3 neurons in the hippocampus stimulates release of glutamate and simultaneously depolarizes the CA3 cells postsynaptically

This leads to activation of the NMDA receptor, which is the coincidence detector for LTP; causes synaptic strengthening such that subsequent stimulations of the pre-synaptic cell cause larger EPSPs

Question 17

How does the NMDA receptor work?

Answer 17

Under resting conditions the NMDA receptor does not respond to glutamate because its ion channel is blocked by Mg2+

Stimulation of the receptor by glutamate which occurs coincidentally with depolarization of the post-synaptic cell results in opening of the channel, allowing Na+ and Ca2+ influx

Ca2+ influx stimulates CAMKII kinase which leads to incorporation of more AMPA receptors in the post-synaptic membrane; CAMKII also self-phosphorylates, causing prolonged activation that lasts for days

Question 18

Which brain areas demonstrate evidence of neurogenesis?

Answer 18

Olfactory bulb (olfactory learning)
Hippocampus (declarative memory/learning)
Cerebelum (procedural memory/learning)

Question 19

What is amyloid protein?

Answer 19

Amyloid B protein (AB) is made by proteolysis from amyloid precursor protein (APP) via the action of B and y secretases

Amyloid is a hydrophobic peptide which tends to self-assemble into long polymers; suspected as the neuropathologic agent in Alzheimer’s

Question 20

What is the role of the amygdala in fear conditioning?

Answer 20

The amygdala receives sensory input from the auditory system (conditioned response) and somatosensory system (unconditioned response, i.e. shock) and sends output to the midbrain reticular formation (freezing behavior) and hypothalamus (increased blood pressure)

Question 21

What is the mechanism of conditioned flavor aversion?

Answer 21

Exposure to food causes cholinergic neurons in the basal forebrain to release ACh in the insular (taste) cortex; muscarinic stimulation of these neurons leads to phosphorylation of the NMDA receptor in the amygdala, which lasts about 30 minutes

Information on malaise from the vagus nerve converges on the amygdala, leading to LTP between the two signals (food and nausea)

Question 22

Role of amygdala in physiology of emotion

Answer 22

Damage to amygdala impairs Pavlovian fear conditioning; subjects exhibit diminished skin conductance response to actual receipt of reward/punishment during Iowa Gambling Test

Suggests that the amygdala plays a role in registering the emotional impact of rewards and punishments

Question 23

Role of ventromedial prefrontal cortex in physiology of emotion

Answer 23

Patients with VMPFC damage lack anticipatory physiologic reaction to impending punishment; also exhibit diminished inhibition of aggression and sexuality but retain normal stress response to actual punishmnet

Suggests that the VMPFC plays a role in anticipating reward/punishment profile of a specific behavior