SPRUSTON, Nelson, Hippocampal Pyramidal Dendritic Plasticity, Janelia, Mar 20, 2014
<p class="MsoNormal" >SPRUSTON, Nelson, Hippocampal Pyramidal Dendritic Plasticity, Janelia, Mar 20, 2014
This is a Thursday, noon, lecture at Stanford in Clark Aud.
in the Neurosci Instit. series.
<b>Prof Spruston is from Janelia Farm campus of HHMI</b>.</p>
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HC = hippocampus is 2% of volume of brain in humans.</p>
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he reviews patient HM Henry Molaison 1926 to 2008 who had
surgery to remove HC for seizures.</p>
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Rodrigues 2002: many animals have HC</p>
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<b>in mice HC is 10% of brain volume</b>!</p>
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we know effects from lesioning;
eg Morris water maze: looking for a hidden platform;
it learns where the platform is...
animals fail to remember the location of platform and
same for multiple arm maze (after lesioning)
<b>John O'Keefe: discovered Place cells</b> that fire when animals is in
certain locations in the maze.</p>
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<b>theta rythm: </b> dynamic rhythm that is always going in HC;</p>
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when <b>mouse is walking it is exhibiting theta rythm</b>
but when it is still it shows <b>SHARP WAVES = SWR</b>.</p>
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<b>Buzaki Lab: local field potential shows theta rythms</b>...</p>
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also see <b>replay of sharp wave ripples</b>
(rapidly... as rehearsal or dreaming... in same sequence)</p>
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<b>HC neurons can keep track of time as well as space</b>...
as mice are running a wheel.</p>
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discusses expt in which mouse turns either R or L and then goes into running wheel
and then goes back into maze... in Buzaki Lab (Eva does work).</p>
<p>
Cuttlefish can remember when to get food (after brief delay or 3 hour delay)
and where to go and what type of food is there (shrimp (which they love) vs crab
which they prefer less).</p>
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<b>HC = hippocampus... how does it work</b>... that is the BIG QUESTION</p>
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my premise: we must understand the properties, connections,
modulation, and plasticity of indiv cell types in the circuit.</p>
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way back in grad school.. he studied dentate cells, CA3 and CA1 cells</p>
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HC was also studied by Ramon y Cajal.</p>
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semi-closed loop to <b>EC = entorhinal cortex</b>.</p>
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Per Anderson Lab... circuits.</p>
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<b>we use HC slices from 3 to 5 week old rats</b>...</p>
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record from cell bodies and the dendrities.</p>
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we also do full neuron models including the dendritic tree.</p>
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Part 2*</p>
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<b>HC pyramidal cell... gets 30K synaptic inputs</b>...
how does it respond to synap input?.</p>
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Nace Golding slide:</p>
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<b>action potentials start near soma but then back propagate into dendritic tree</b>...</p>
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dendrites generate action potentials but they fail to propagate all the way to soma.</p>
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but two dendr action potentials they can propagate spike all the way to the soma.</p>
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dendrite is v small diameter,,, so easy to gen a spike
but that current is not enough
once it hits a big volume trunk (cuz the EPSP is diluted).</p>
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<b>why have dendritic spike if they cannot propagate?...</b>
<b>cuz they are impt for LTP</b>.... depends on spikes gen in dendrites.</p>
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what type of dendr spikes mediate LTP?</p>
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candidates: Na spike, Ca spike and NMDA spikes....</p>
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<b>can get LTP even with NO spikes from soma</b>!!!</p>
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Challenges for the field:</p>
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do dendrit spikes occur naturally in vivo? he thinks YES.</p>
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how do dendrit trees integr and compute?
is it the same in HC and other systems? maybe.</p>
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how does neuromodulation affect this?</p>
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diversity of HC pyramidal cells*</p>
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he shows</p>
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<b>principal excitatory cells... abt 7 types
(and dozens of interneuron types</b>)</p>
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difference btwn <b>regular spiking pattern versus bursting pattern</b>...
eg in pyram neurons in CA1 and subiculum...</p>
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Austin (in his lab) did voltage clamp recordings in many difft cell types...</p>
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he showed that there are indeed two difft groups of cells...</p>
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<b>bursting versus regular spiking cells</b>; there are both types in both CA1 and subiculum.</p>
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can even see morphologic differences...</p>
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regular spiking cells have many branches at base (dendr going into soma)
versus the apical dendrites in bursting cells.</p>
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renamed these <b>LATE bursting versus EARLY bursting </b>...
( in relation to when current is injected)</p>
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Jim Knierim 2006 detailed diagram of HC</p>
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may be difference btwn proximal (close in cues) vs distal cues
(ie cues that are physically close to the animal vs far away
(eg distant exit signs in Clark Aud)</p>
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Plasticity of Excitability of neurons in HC*</p>
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<b>TBS = theta burst stimulus</b>... changes excitability of neurons...</p>
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depends on muscarinic cholinergic receptors.</p>
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he shows bursting in reponse to TBS...</p>
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incr in bursting requries <b>mGluR1 and mAChR = muscarinic ACh receptor</b>.</p>
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get exactly oppositive results in LATE bursting cells (vs EARLY bursting cells)</p>
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he returns to Knierem 2006 diagram of HC...
which shows <b>two paralell processing channels</b>
(<b>one for distal cues and one for proximal cues</b>)</p>
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mGluR metabotropic Glutamate receptors...</p>
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so, there is synergistic modulation by glutamate and ACh receptors...</p>
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must have both ACh and metabotropic glutamate.</p>
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Huge Lab... he just moved to Janelia Farm (from Northwestern).</p>
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so, big Q: how does it ALL work (in HC)</p>
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he has shown props of princ neurons: CA1 pyram and subiculum pyrams...</p>
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Mark Cembrowsky at Janelia (post doc)</p>
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do RNA labeling of HC cells ...</p>
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want to understand difft transcriptional profiles in difft cells.</p>
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want to find partic genes that are differentially expressed eg in particular CA1 cells.</p>
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Erik Bloss: using array tomo (a la Coleman/ Smith) to get entire CA1 dendritic tree.</p>
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look for co-localization of synaptophysin and presynap structures to find synapses...</p>
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end</p>
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Q1 mech of bursting? post translation of channel types that
determine post synap spiking thresholds.
prob. has to do with the kind of info that cell is integrating
(whether it is a late or early burster)</p>
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distinction btwn dorsal vs ventral HC?</p>
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No difference btwn CA1 and subiculum in cell types...
may just be reasonable to simply talk abt output neurons from HC.</p>
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</p>