Memory and Neuroplasticity Notes

Sensory Register:
- Vision: Retains information for approximately 1 second.
- Auditory: Retains information for about 5 seconds.
Short Term Memory:
- Duration: Holds information for roughly 30 seconds.
- Capacity: Limited to 7 ± 2 items, with displacement occurring as new information arrives.
Long Term Memory:
- Mechanism: Relies on synaptic modification.
- Characteristic: Considered timeless.
Working Model for Memory:
- Involves different sensory modalities: visual, auditory, olfactory, and gustatory.
- Rehearsal and consolidation processes are crucial.
- Central executive functions play a key role.

Synaptic Transmission:
- Normal synaptic transmission involves the release of glutamate (Glu) from the axon terminal.
- Glial cells surround the synapse.
- The synapse contains NMDA and AMPA receptors.
- NMDA receptors are initially inactive due to a magnesium ion ( $Mg^{2+}$ ) block.
- AMPA receptor activation leads to cell depolarization.
Learning and Memory:
- Latent AMPA receptors are present.
- Activation of protein kinases like CaMKII, PKC, and TK.
- CREB (cAMP response element-binding protein) is involved in the process.

Physiological Changes:
- Changes at the synapse can store information.
Structural Changes:
- Changes at the synapse may provide long-term storage.
- Memory formation requires protein synthesis.

Physiological Changes:
- Occur at the presynaptic and/or postsynaptic neuron.
- Include increased neurotransmitter release or enhanced receptor effectiveness.
Anatomical Changes:
- Store memory at synapses.

Strengthening Synapses (LTP):
- "Neurons that fire together wire together."
- If the presynaptic axon and postsynaptic neuron are active simultaneously, the synapse is strengthened.
Weakening Synapses (LTD):
- "Neurons that fire out of sync lose their link."
- If the presynaptic axon is active but the postsynaptic neuron is inactive, the synapse is weakened.

Experimental Setup:
- Rats were raised in three environmental conditions:
  - Standard Condition (SC)
  - Impoverished Condition (IC): Isolated
  - Enriched Condition (EC)

Dendritic Structure:
- Apical dendrites
- Basal dendrites
Impact of Environmental Conditions:
- Enriched Condition promoted more dendritic branching compared to Standard and Impoverished Conditions.
- The order of branch affects the mean branches/neuron.
- The rats in Enriched Condition had the most mean branches/neuron, followed by Standard Condition, and then Impoverished Condition.

Animals in Enriched Conditions (Manhattan):
- Increased AChE activity (thicker cortex, especially occipital).
- Increased dendritic branching (especially basal dendrites).
- Increased synaptic contacts (dendritic spines and synaptic size).
Behavioral Benefits of Enriched Experience:
- Promotes better learning and problem-solving.
- Aids recovery from conditions such as malnutrition.
- Protects against age-related decline in memory.

Early Enriched Experience:
- Reduces cortisol levels (preventing hippocampal atrophy), facilitating better response to stress.
- Prompts nerve growth factor expression in the hippocampus, preventing hippocampal degeneration.
- Enlarges neural networks, buffering against synapse loss during aging.
Late Enriched Experience:
- Living in active environments and participating in cognitive activities reduces cognitive decline.

Mechanism:
- Presynaptic neurons produce a high rate of action potentials.
- Postsynaptic neurons respond with larger EPSPs.
- Results in a stable and enduring increase in synaptic effectiveness.
Tetanus:
- Brief electrical stimulation that triggers thousands of axon potentials.
- After tetanus, EPSPs remain high for hours.
Role of Hippocampus:
- The hippocampus is the most important structure for LTP.

Initial Activation:
- Glutamate first activates AMPA receptors.
- NMDA receptors do not respond initially; they require sufficient AMPA receptor stimulation to partially depolarize the neuron.
- NMDA receptors are blocked by a magnesium ion ( $Mg^{++}$ ) at rest.
Glutamate and LTP:
- The most-studied form of LTP uses glutamate as a transmitter and depends on both NMDA and AMPA receptors.
Normal Activity:
- During normal activity, glutamate released at CA1 synapses activates only AMPA receptors.

Depolarization:
- After partial depolarization, the magnesium block ( $Mg^{++}$ ) is removed from the NMDA receptor.
- The NMDA receptor allows calcium ions ( $Ca^{++}$ ) to enter in response to glutamate.
Protein Kinase Activation:
- The large influx of calcium ions ( $Ca^{++}$ ) activates protein kinases, which phosphorylate and activate other molecules.
Changes in AMPA Receptors:
- Existing receptors move to the active synapse.
- Increased ion conductance.
- More receptors are produced.

Increased AMPA Receptors:
- The increased number of AMPA receptors in the membrane unblock more NMDA receptors.
Short-Lived Upregulation:
- AMPA upregulation is short-lived.

CREB Activation:
- CREB (cAMP response element-binding protein) binds to DNA promoter regions.
Gene Transcription:
- CREB changes the transcription rate of genes.
- These genes produce proteins that change synapse structure and contribute to LTP.
Role of Protein Kinases and Dendritic Spines:
- Protein kinases and dendritic spines are integral to this process.

Inducible cAMP Early Repressor (ICER):
- ICER makes CREB antagonists.
- These antagonists compete with CREB for binding sites, disrupting the formation of long-term memories.

Mechanism:
- Increased calcium ( $Ca^{2+}$ ) concentration activates protein kinases.
- Induction of LTP activates a retrograde signal for the presynaptic neuron to release more transmitter.
Retrograde Messengers:
- Examples: NO (nitric oxide), arachidonic acid, and others.

LTP Increases Synaptic Effectiveness By:
- Increasing postsynaptic receptors.
- Increasing transmitter release.
Research Implicates LTP in Memory:
- Pharmacological treatments that block LTP also impair learning.
- Mice that overexpress NMDA receptors have enhanced LTP and better long-term memory.