PKC and ZIP in Late LTP

Retrograde Alteration

• Interventions that alter the spatial distribution of synaptic efficacy can change an animal's memory of a prior learning experience.
• An atypical isoform of PKC (protein kinase Mzeta) is active only in late LTP, and an inhibitor (ZIP) of this isoform has been discovered.
• ZIP works as a pseudosubstrate, preventing the enzyme from recognizing its real ligand.

Experiment with ZIP

• Electrophysiological experiment: high-frequency stimulation was delivered, causing synaptic potentiation, and then ZIP was applied, leading to downregulation of synaptic potentiation.
• Behavioral experiment: Place avoidance apparatus was used, and animals treated with ZIP lost the memory of the dangerous situation.

Mimicry

• The possibility of creating a false memory through artificial manipulation of synapses.
• Two problems to solve:
  • How to artificially potentiate specific synapses in the brain (optogenetic approach).
  • How to identify synapses undergoing LTP during learning (in the amygdala).

Chloride Cotransporters

• NKCC1 (Na-K-Cl cotransporter type 1): uses energy from sodium extrusion to allow chloride entrance into the cell, increasing [Cl]i.
• KCC2 (K-Cl cotransporter type 2): exploits the potassium gradient to pump chloride out of the cell, decreasing [Cl]i.
• In immature neurons, NKCC1 is more expressed, leading to chloride accumulation; during development, KCC2 expression increases, and NKCC1 remains invariant.

GABA's Role

• GABA can have a depolarizing or hyperpolarizing role, influencing the action potential.
• In immature neurons, GABA has a depolarizing activity, switching to hyperpolarizing in mature neurons.
• GDPs (giant depolarizing potentials) are influenced by GABA's excitatory action.

Synaptic Plasticity

• Experience-dependent modification in strength of neuronal communication, relying on synaptic changes.
• Types of plasticity: LTP/LDP, short-term/long-term, NMDA-dependent/independent.
• Synaptic plasticity is related to the past history of the subject being analyzed, similar to memory.