Limbic System, Learning, Memory, Amygdala

Ability to recall events/facts that have a specific temporal and spatial context, also includes semantic knowledge

Ability to learn new skills

Declarative memory, get anterograde amnesia

Procedural memory

lasts for fractions of a second to seconds, most sensory systems include this type of memory and the process underlying this type of memory takes place in sensory cortex

Lasts for seconds to minutes, like when you are making enchiladas and need to remember if you added salsa or not. Takes place in frontal cortex

memory that lasts for days or years, stored in neocortex, starts in hippocampus

Working memory

fMRI indicates that this is where long term declarative memories are stored. Lesion analysis also shows this

He had bilateral hippocampal lesions. Both the amygdaloid complex and the entorhinal cortex were affected.

Because this is important in the formation of declarative memory, his ability to form new declarative memories was affected. He could not recall events or facts that happened in the short term, as well as new semantic knowledge

Associative memory is learning to associate cues with a particular fact or object. For example, when you're playing charades, at first you may not be very good at knowing that a particular cue means English or Hindi, but as you get better, you learn to recall the difference with a smaller number of cues. LTP is required for this to happen

Coincidence detection (depolarization AND glutamate activation), if both occur simultaneously, the NMDA receptor opens and Ca enters and more AMPA receptors are embedded in the membrane. For example, Pavlov's dog smelled food AND heard a bell at the same time. When he smelled food, a neuron was depolarized, when he heard the bell, glutamate was released.

Eventually the bell and the beef were associated

Ca phosphorylates Cam Kinase 2, when it is phosphorylated it keeps phosphorylating itself and ultimately causes AMPA to become embedded in the post synaptic membrane

LTP takes place at CA1 and CA3 neurons during a tetanic burst. Glutamate AND depolarization must occur at these synapses

If you measure voltage at CA1/3 when stimulated at high frequency, see large EPSP and stay "on" for long time. This is because presynaptic neurons release glutamate which binds to AMPA. This depolarizes the post synaptic neuron. When it has depolarized enough, Mg from the NMDA receptor becomes unplugged, gets bound by glutamate and allows Ca to come in.

When Ca comes in, it binds CK2 which brings in AMPA receptors and strengthens the PS response

Synapse formation occurs in the adult brain, and neurogenesis occurs in the olfactory bulb, cerebellum and hippocampus

APP is cleaved by alpha under normal circumstances, in AD it is cleaved by gamma or beta resulting in fragments which aggregate to form Amyloid plaques

Failure to maintain LTP, impaired spatial memory. So maybe reducing levels of Abeta peptide in early AD or inhibition of the proteases that cleave it incorrectly

Amygdala is involved in associative learning involving painful or harmful stimuli (foods, mechanical stimulation or loud noises) Lesions here cause animals not to respond appropriate to potential threats. They also cannot process emotions like fear/anger

Coincidence detection between two flavors or coincident olfactory/taste information. Ach is released in the insular/taste cortex in response to a novel food and this binds to muscarinic receptors which may modulate CFA

Phosphorylation of NMDA receptors affects fibers coming from the amygdala.

This takes place a little while after the actual food stimulus suggesting that associative learning can take place when the stimuli are not simultaneous

Ach is important in memory consolidation as well. So this is why cholinergic agonists help early AD. Unfortunately, AD grows to affect more than cholinergic system in its later stages.