Lecture 29: Learning and Memory Basic Mechanisms (Vertebrate Systems)

What did Cajal speculate about how information was stored?

that information storage in the brain results from alteration in synaptic connections between neurons (neural circuit)

What did Hebb believe when it came to information storage?

memory results from synaptic modification

What did Donald Hebb’s the Organization of Behavior state?

persistent activation of a group of simultaneously active neurons would lead to consolidation of stronger connections

What can neurons do in response to extrinsic stimuli?

can change and adapt the strength of their connections. Ex. LTP and LTD

What helps correlate cellular learning and memory?

• associative

• rapidly induced

• input specific

• positive feedback process

• physiological relevance

What is the key to forming declarative memories in the brain?

LTP and LTD

Where are axon 1 and axon 3 located in the hippocampus?

• axon 1: perforant pathway of major axons from EC to DG

• axon 3: schaffer collateral of major axons from CA3 to CA1

In the Bliss & Lømo experiment, which pathway was stimulated?

Perforant path from the entorhinal cortex

What distinguished the experimental (Exp) pathway from the control (Cont) pathway?

Exp received high-frequency conditioning stimulation; Cont received only basal stimulation

After repeated conditioning, roughly how large was the Exp population EPSP compared with baseline, and how long did it last?

~300%, for hours

In the extracellular traces, how can you tell a synapse has been potentiated?

The downward deflection gets deeper

What does 'input specificity' of LTP mean?

Only the synapses that received HFS are potentiated; other inputs to the same neuron are unchanged

Which stimulation pattern produces LTD?

Low-frequency stimulation (LFS)

During the LTD experiment, what happened to Input 2, which received only basal stimulation?

It stayed at baseline, so LTD is input-specific

What happens during the Passive (Inhibitory) Avoidance Test?

• exploits a natural tendency of mice to enter dark environment

• the mice learn to avoid a mild aversive stimulus by remaining in the lighted side of a two-compartment chamber and not entering the dark (unsafe) side

• record the median step-through latency (before subjects cross into the unsafe side of the chamber)

• record the % of animals from each test group that crosses the threshold within the time allowed

What is inhibitory avoidance (IA) learning?

A rat learns to avoid a chamber where it received a foot shock

In Whitlock et al., what was measured to track synaptic strength?

fEPSP slope across an 8-electrode array in CA1

After IA training, did every electrode show increased fEPSP slope?

No, only a subset of electrodes showed a lasting increase

Which group showed a persistent increase in fEPSP slope?

IA-trained

What does 'occlusion' mean in this experiment?

Learning-induced potentiation leaves less room for later HFS-induced LTP, because both use the same mechanism

After renormalizing the baseline and giving HFS, which pathway showed larger LTP?

The untrained pathway

Why is the occlusion result important?

It is strong evidence that learning in the brain uses the same mechanism as LTP

What is the problem with Hebbian Plasticity?

eventually neural networks will reach extreme and become unstable

What is homeostatic plasticity?

rapid or prolonged process to maintain neuronal firing and synaptic strength within physiological limit, thereby preventing unrestrained increases or decreases in neuronal activity

What is true of the neuronal environment?

there are constant and dynamic changes in their activity in response to overwhelming sensory information and other stimuli

What are the boundaries of the physiological limit of homeostatic plasticity?

• induced rapidly or in a long-term

• global but unequal scaling

• homeostatic negative feedback process

• physiological relevance

  • developmental regulation

  • excitatory-inhibitory balance in vivo (intraocular injection of TTX or dark rearing)

  • connection-specific regulation (TTX effect on CA3-CA1 versus CA3-CA3)

  • abnormal plasticity in disease mechanism

What is the main function of homeostatic synaptic plasticity?

To keep a neuron's overall activity in a stable range

What does mEPSC amplitude mainly reflect?

The number of postsynaptic AMPA receptors

What happens after prolonged sensory or activity deprivation?

mEPSCs get larger and AMPA receptors are added (scaling up)

What happens after prolonged sensory or activity enhancement?

mEPSCs get smaller and AMPA receptors are removed (scaling down)

How does homeostatic plasticity differ from Hebbian LTP?

Homeostatic plasticity is negative feedback; LTP is positive feedback

On what timescale is homeostatic plasticity induced?

Prolonged treatment, over hours to days

What are the two broad ways plasticity can change a neuron's output?

Changing synaptic transmission and/or intrinsic excitability

What is intrinsic excitability?

A neuron's propensity to fire action potentials

In Mozzachiodi & Byrne's 'nonsynaptic' example, what changed after learning?

The presynaptic neuron fired two spikes instead of one to the same stimulus; the synapse was unchanged

What does the population spike measure, compared with the population EPSP?

Summed action potential firing of many cells

After HFS in Bliss & Lømo, what happened to the population spike?

Amplitude increased (~200%), latency decreased (~4 → 3 ms)

In the epilepsy study, why was synaptic transmission blocked?

So any difference in firing had to come from intrinsic properties

How did CA1 neurons from epileptic animals fire compared with sham controls?

Bursts of clustered spikes instead of regular single spikes

What do WDR, LT, and HT stand for in dorsal horn neurons?

Wide dynamic range, low threshold, high threshold

After spinal cord injury, what notable change appeared in high-threshold (HT) neurons?

They began responding to brushing and responded more strongly to pressure and pinch

In homeostatic intrinsic plasticity, how does prolonged activity deprivation change firing to the same current step?

More spikes: excitability increases

How can you induce intrinsic plasticity?

ion channels

What are the two main mechanisms of intrinsic plasticity?

Changing ion channel distribution and density, and changing ion channel biophysical properties

Where are I_h (HCN), I_K,A (Kv4.2), and I_Ca,T (Cav3.2) channels most concentrated in a CA1 pyramidal neuron?

Distal dendrites, increasing with distance from the soma

Which channels are concentrated at the axon initial segment and nodes of Ranvier?

I_M (Kv7), I_NaP, and I_K,DR (Kv3.1)

How is Kv2.1 distributed in the figure?

In clusters (patches) in the apical dendrite and soma

Why does an uneven distribution of ion channels matter for plasticity?

Adding, removing, or moving channels in a compartment changes how that region handles inputs and how readily the neuron fires

What does a voltage-gated channel open in response to?

A change in membrane potential