Lecture 35- Neuronal plasticity III

Question 1

Where is the hippocampus, what is it affected by and what is its major role?

Answer 1

• Medial temporal lobe (has three layers, the pyramidal cells one layer, these are the important ones for communication, send long projections to other parts of the brain, under control by local interneurons, these have short axons)
• Part of cerebral cortex, but not neocortex
• Severely affected in Alz. Disease, the whole medial temporal area is severely affected (as well as cholinergic neuromodulary system in the forebrain), these cholinergic neurons pretty much drive the hippocampus
• Circuitry: “The Trisynaptic circuit”
• Major role in memory function - consolidation of STM to LTM - crucial in spatial memory
• learning a motor skill involves mainly cerebellum
• the sort of memories that the hippocampus deals with are declarative and episodic as well as semantic and spatial
• hippocampus consolidates the memories (from short term into long term)
• not a global spot for memory but important for many aspects, if you remember everything it becomes and impediment

Question 2

How does memory processing work in the hippocampus?

Answer 2

• episodic memory is a combination of auditory, visual etc.
• that memory is polymodal association memory, comes from the frontal, temporal and parietal lobes
• if it is to be rememebered is has to go through the hippocampus
• the gateway to it is the entorhinal cortex (also affected by Alzheimer’s), this packages the story to be remembered
• this info comes to the hippocampus via the entorrhinal cortex, the classic trisynaptci circuit consists of these 3 synaptic junctions, firstly where the entorrhinal cortex synapses with the dentate gyrus (semantic memory), this is part of hippocampal formation but not hippocampus, the dentate gyrus is the entry point to the hippocampus (PERFORANT PATHWAY!)
• then from the dentate gyrus (where is is granular cells) then form a second synapse with CA3 hippocampal neurons, this is important as these are the mossy fiber axons (dentate into CA3), these are powerful, also called teacher synapses
• the third synapse is from CA3 to CA1 neurons, these are the Schaffer Collateral pathway
• each of the synaptic connections has a name, perforant, mossy fibre and schaffer collateral pathway
• from CA1 then project out of the hippocampus, close to where the info originated via the subiculum (relay station) to entorhinal cortex, then goes to the cortex and we remember it for a longer time

Question 3

What is the trisynaptic circuit of the hippocampus?

Answer 3

• this is the rat brain
• has the same circuitry as in the human, the perforant pathway then the Mossy fibre pathway and Schaffer collaterals then back to entorhinal cortex via teh subiculum

Question 4

What does the transverse section of the hippocampus look like?

Answer 4

• this is in a human
• the grey is the outline of the medial temporal cortex (lobe)

Question 5

Transverse section 2:

Answer 5

• numbers show the order in which the information is passed through this circuit
• new information coming in from the entorrhinal cortex
• then through the perforant pathway to the dentate gyrus
• then mossy fibre to CA3
• then Schaffer collateral to CA1, then to subiculum and then back to entorhinal cortex, the information is altered and will be stable over time
• hippocampus consosts of the blue areas, the second infolding of the medial temporal lobe
• subdivided into 3 or 4 regions, CA1, CA2, CA3 (and sometimes CA4)
• only CA1 and CA3 are important in this circuit
• the fambria fornix is a little projection coming to the hippocampus which is from the cholinergic neurons in the forebrain, the hippocampus is dependant on this input

Question 6

What is the mossy fiber teacher hypothesis?

Answer 6

1. One mossy fiber is activated resulting in the CA3 pyramidal neuron firing
2. A back propagating AP travels the length of the dendrite
3. Activated pathways temporally linked to the CA3 AP are potentiated

Question 7

What is the memory processing via the hippocampus?

Answer 7

-mossy fibre is onto the CA3 neurons

Question 8

What is the memory processing via the hippocampus with weak or strong input?

Answer 8

• this is maybe how the association works, via the mossy fibre input, depending if strong or weak and the timing of these inouts is also important
• similar thing happening in CA1 neurons, strin input from CA3 and weak input form entorhinal cortex

Question 9

What is a functional and silent synapse?

Answer 9

-silent synapses have only NMDA receptors, but they have lot of AMPA receptors waiting close by, once these are inserted then it bceomes and active synapse

Question 10

What is the early and late LTP like?

Answer 10

• early is just chemcial phosphorylation
• later phase involves creation of new contacts but not that much later, only half an hour or so

Question 11

What are the mechanisms responsible for long-lasting changes in synaptic transmission during LTP?

Answer 11

-one hour after stimulation, get two new dendritic spines here so it shows that LTP late phase has occured! learning

Question 12

What is the postsynaptic depression in the hippocampus like?

Answer 12

• LTD
• you can make it happen by 15 min low frequency transmission, the synapse gets weaker here as it is underused for a long time and the connection gets less strong

Question 13

What are some examples of plasticity in brain function?

Answer 13

• Treatment of chronic pain syndromes
• the use of NMDA antagonists to reset aberrant circuit behaviour
• NMDA antagonists and treatment-resistant depression; resetting
• can change the behaviour and patterns of activity, in chronic pain for example, can do this via blocking NMDA receptors so mute the circuit
• in depression that have resisted treatment can respond to NMDA blockage in the brain