Lecture 15

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University of Toronto St. George
Cell and Systems Biology
Melanie Woodin

CSB332H1S L15; March. 12, 2012 Inhibitory Synaptic Plasticity in the Hippocampus Watch online:  http://www.pbs.org/saf/1402/video/watchonline.htm  Interviewing patient EP – lost hippocampi selectively due to a virus o Also tissue immediately around it  Interviewed almost weekly since  Deep in temporal lobe, so hard to remove without damaging other structures  Also no neurogenenerative disease that results in only this loss  EP – now 82; acute virus in 1992, more thinking skills virtually intact o Can copy complex drawings, read back list of words, amazed at laptop o Repeats self often & unaware (was in electronics, computers used to fill a room) o Enjoys the expts, unsure if met expt’ers before, can’t remember names even though visited over 200 times o Has a record of the experiences – been positive, lets expt’ers inhat determines the strength of inhibitory synapses? door faster, built repor’ w expt’ers  Synaptic conductance depends on: o amt of transmitter release o Can’t rmbr 15mins ago o # & conductance of postsynaptic transmitter recs (GABA A) o Can remember childhood vividly (ex. how to get places, remembering streets & directions, maps)  Driving force for Cl-  So hippocampus can’t be where memories permanently o Specific for GABA A stored, but crucial for recording new memories o If levels rise  reverses pot of GABA above resting pot, so depolarized  But does not know streets where he currently lives  In all organisms examined to date, have developmental changes in levels of Cl – esp in first 2 weeks after birth (postnatal development, goes lower) o In pathological disorders (ex. schizophrenia) Cl higher o No evidence that other ion grads affect these  driving force  (E GPSCr ECl  Hippocampus required to store long-term memories  LTP = model of cellular basis of memory Synaptic plasticity occurs at both excitatory & inhibitory synapses  Classic excitatory glutamatergic long-term potentiation has been well characterized in numerous systems  Inhibitory synaptic plasticity has been less well-characterized despite its known roles in regulating neuronal network activity  We determine the strength of GABA -Aediated synaptic transmission by measuring the reversal pot for GABA (EGABA); GABA is the value of Long-Term Objectives of the Woodin Lab the membrane pot where there is no net flow of Cl- ions thru the  To determine how electrical &physiological activity in the brain GABA rAc modifies inhibitory synapses (termed inhibitory synaptic plasticity)  What are the mechanisms underlying inhibitory synaptic plasticity  To understand how inhibitory synaptic plasticity contributes to: o the cellular basis of learning & memory, and o information processing in the brain  fn’al significance of inhibition in laying down memories GABA RAceptor  Ligand-gated ion channel  Largely permeable to Cl-  Contains numerous binding sites for allosteric modulators  GABA not always inhibitory but main inhibitory in adult CNS  Glycine also inhibitory but more often found in spinal cord, rec similar  3 types, A & B most common  A = ionotropic, mostly permeable to Cl, also permeable to bicarbonate o Many endogenous binding sties for allosteric modulators  Barbiturates, steroids  B = metabotropic  signal cascade  open K channels  Balena & Woodin 2008 European Journal of Neuroscience  What changes in reversal pot for GABA – determined by level of Cl  Depolarization at first  switch in fn of GABA since Cl levels drop dramatically, so hyperpolarized  CA1: feedforward inhibition o Axons fire act pots down Schaffer Collateral to pyramidal in CA1 o Also fire to interneurons (in CNS are normally inhibitory, contain
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