\documentclass{seminar} \usepackage{colordvi} \begin{document}
Types of synaptic plasticity in the neocortex
\begin{center}\emph{What is the synaptic basis of plasticity in neocortex}\end{center}
Three possible interpretations of my question:
- molecular mechanisms \begin{scriptsize}("the basis of synaptic plasticity")\end{scriptsize}
- \textbf{overview of types of synaptic plasticity \begin{scriptsize}("the basics of synaptic plasticity")\end{scriptsize}}
- synaptic plasticity and learning \begin{scriptsize}("the basis of learning")\end{scriptsize}
Contents:
\begin{itemize} \item Short term plasticity \begin{itemize} \item Depression \item Facilitation \item Augmentation and PTP \end{itemize} \item Synaptic scaling \item Long term plasticity \begin{itemize} \item STDP \item Different STDP rules \item theta burst induced LTP \item pairing protocol LTP \item LFS-LTD \item Synaptic redistribution \end{itemize} \end{itemize}
Short term synaptic depression
- Activity $\to$ reduction of later EPSCs
- Can be modified by LTP (synaptic redistribution)
\includegraphics[scale=.7]{depression.eps}
\emph{EPSCs during 50 hz train in PFC, layers III$\to$V }
\bigskip
Mechanisms \RawSienna{\begin{scriptsize}(by analogy with other areas)\end{scriptsize}}
- Presynaptic
- Reduction of \# of quanta released by a presynaptic spike
- depletion of pool of readily releasable vesicles
Facilitation
- Activity $\to$ increase of later EPSCs
- Paired-pulse facilitation
\bigskip
Mechanisms \RawSienna{\begin{scriptsize}(by analogy with other areas)\end{scriptsize}}
- Presynaptic
- Increase in \# of quanta released by a presynaptic spike
- Residual Ca$^{2+}$ hypothesis
Depression vs. facilitation
In neocortex, usually, but not always, depression wins. Example:
\includegraphics[scale=.7]{depressionVsFacilitation.eps}
\emph{2nd fPSP and 15th fPSPs in PFC as a function of stimulation frequency, layers III$\to$V }
seemingly longer decay time constant of depression
Augmentation and PTP
- Like a longer-timescale version of facilitation
- Augmentation about 7 sec, PTP about 60 secs
- Probably both of them in neocortex, but haven't been differentiated too well yet
- Only in some regions (e.g. mPFC, but not visual cortex)
\includegraphics[scale=.7]{augmentation.eps}
\emph{EPSCs in PFC after a 15 stimulus, 50hz tetanus, layers III$\to$V }
Augmentation and PTP cont'd
Mechanisms \RawSienna{\begin{scriptsize}(by analogy with other areas)\end{scriptsize}}
Similar to facilitation: presynaptic, increase in \# of quanta released by a presynaptic spike, residual Ca$^{2+}$ hypothesis
Synaptic scaling
- Over 2 days, less activity $\to$ greater synaptic strength
- The opposite happens with more activity
- Scaling is proportional to synaptic strength
\includegraphics[scale=.8]{synapticScaling.eps}
\emph{cultured pyramidal neurons from visual cortex}
Synaptic scaling cont'd
Mechanisms
- bigger mEPSCs
- $\exists$ postsynaptic component: puffed glutamate has greater effect after scale up
- Not NMDA-dependent (AP5 doesn't block)
- AMPA-dependent (CNQX blocks)
STDP
- Block GABA_A with bicuculline (not necc. req'd)
- Current clamp used to evoke spikes in presynaptic and postsynaptic cells
- Relative timing of pre- and post-: on the order of 10-500 ms
- Repeat 100 times at around .2 Hz
- Quantified as amplitude of EPSP slope ratio
\includegraphics[scale=.6]{stdpRules.eps} \textbf{STDP cont'd: Different STDP rules}
STDP cont'd: Different STDP rules
\includegraphics[scale=.6]{rateTimingCurves.eps}
STDP cont'd: Mechanisms
- where's the coincidence detector?
- 1 or 2?
- NMDA receptors and calcium timecourses
- dendritic spike backpropagation enhanced superlinearly by prior EPSPs via Na channels
\includegraphics[scale=.6]{dendriticNaChannels.eps}
STDP cont'd:
Mechanisms
calcium level $\to$ sign of plasticity? Or where the calcium enters important, too?
\includegraphics[scale=.6]{calciumLevelMystery.eps}
STDP cont'd:
Mechanisms
- multiple calcium pools?
- presynaptic coincidence detection?
STD-LTP
- NMDA $\to$ Ca$^{2+}$ $\to$ CaMKII? $\to$ \ldots
- NMDA receptor dependent
STDP cont'd:
Mechanisms
STD-LTD
- L-type Ca$^{2+}$ channel $\to$ Ca$^{2+}$ $\to$ Calcineurin? $\to$ \ldots
- Not NMDA-receptor dependent on postsynaptic side (internal MK801 blocks postsynaptic NMDA receptor, but not STD-LTD)
- But AP5 extracellularly blocks, so NMDA is req'd somewhere\ldots
- presynaptic CB1 receptors req'd (STD-LTD blocked by AM251, a CB1 antagonist)
theta-burst LTP
10 bursts of 10 pulses at 100hz bursts, 15 secs in between bursts
\bigskip
Mechanisms
- NMDA-dependent form exists
- Non-NMDA dependent form exists (at least) in L2/3 visual cortex
pairing protocol LTP
pair EPSP with postsynaptic depolarization
\bigskip
Mechanisms
- NMDA-dependent form
- \RawSienna?{\begin{scriptsize}(by analogy with other areas)\end{scriptsize}}: CAMP-PKA-MAPK-CREB
- NMDA-independent form (at least in juvenile visual cortex)
- Silent synapses
LFS-LTD
1 hz, 900 sweeps
\bigskip
Mechanisms
- Less Ca$^{2+}$ entry?
- Postsynaptic NMDA receptors not req'd
- CB1 receptor req'd
Synaptic redistribution
- An effect of (NMDA-dependent, pairing protocol) LTP on short-term plasticity
- Effect of LTP in cortex has increases amplitude of first few EPSPs
- But does not affect amplitude of steady-state EPSPs (at high frequency)
- (at low frequency, steady-state amplitude is increased)
\bigskip
Mechanisms
Hypothesis: potentiation via increase in probability of release (presynaptic), but depression from more depletion of readily releasable pool
Bibliography
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