DOMBECK, Daniel, Spatial Navigation Grid and Place Cells, Northwestern, Oct 22, 2015
<p class="MsoNormal" >DOMBECK, Daniel, Spatial Navigation Grid and Place Cells, Northwestern, Oct 22, 2015</p>
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(This was one of my favorite talks of the quarter; Dan images not only spiking in whole
HC CA1 cells, but also in their dendrites (the "regenerating events.")
(If you're a beginner, look at his video on YouTube.)</p>
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how are these representations (of place fields) formed and maintained in time (studied in his lab)</p>
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grid cells (ERC= entorhinal cortex)
place cells in HC (downstream from ERC</p>
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Nobel Prizes just awarded for this work.</p>
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<b>HC place cells, spatial memory and Hebbian Potentiation.</b>..</p>
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precision of place fields (means SMALL in relation to the site that the animal is in.)</p>
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and stability of place fields (over time)</p>
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NMDA1 CA1-KO in mouse leads to NMDA block and leads to imprecise place fields
and unstable place fields...</p>
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and is this relevant to animal navigation...yes...</p>
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eg cannot find exit point of a circular maze...
they are impaired on spatial memory tasks as per Tsient in 1996.</p>
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so, what are the NMDA receptors actually doing in these tasks.... <b>coincidence detectors...</b></p>
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you need both <b>glutamate release and strong depolar at post synaptic</b> depolarization
(and calcium entry postsynaptically)</p>
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backpropagating APs in Magee and Josnston in 1997</p>
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and dendritic spikes in Golding 2002...</p>
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global plasticity signal... (backprop the signal thru the entire arbor</p>
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and also differential plasticity signals (in only some dendrites....</p>
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(how do these regenerative events mediate place cells mechanisms.) his lab's focus.</p>
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branch spikes as regenerative events...</p>
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we cannot disting. backprop fromm spiking events in dendrites.</p>
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he was post doc with David Tank....(and uses similar rodent set ups)</p>
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<b>mouse on styrofoam ball... </b>say, suspended on air...
looks at VR screen...</p>
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1934 Uexall also had this idea...</p>
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shows <b>great YouTube</b>...(of mouse in VR maze on Tank ball)</p>
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Two-photon imaging of place cell soma and dendrities.</p>
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navigation system is being activated in these animals in robust way...</p>
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mouse looks at huge TV in front of him... get this YOuTube.</p>
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uses GCAMP6f... uses 2 photon imaging of place cells soma and dendrities.</p>
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calcium transients are due to action potentials = APs</p>
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can use electic lens to change focal plane; can change Z</p>
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we can hop back and forth from cell to spines.</p>
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compares shaft transiet to spine transiet in a regenerative branch spike event.</p>
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shaft spike (in calcium image ) might be use to 3 backprop spikes.</p>
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sees huge spine transients (when get glutamate release and simult.
backprop regen event.(regenerative branch event)</p>
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we can <b>disting "regenerative events in the dendritic arbor" and spike events.</b> key point.</p>
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he shows that can get these separately in a firing place cell..
. ie the surrounding dendrites need not be having regenerative events.</p>
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records from ONE cell at place field 1 and place field 2.</p>
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he answers me.... two traversals with difft responses of one place cell...</p>
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across off place cells the fire about 53% of time with dendritic regen events (alll branches)</p>
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21% some branches and 27% soma only of place cell but NO regen events in the basal arbor) why? mystery...</p>
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who... what are these mechanisms underlying....</p>
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branch alone ... might be due to dendr spike.</p>
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soma alone might be perisomatic inhibiton or Na channel stuff.</p>
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everything in dendr arbor is prob dendritic spikes rather than backprob from soma.</p>
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can also rarely get no spike in soma but get spikes in all dendrites (not due to backprop)</p>
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summary...</p>
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1) dissoc btwn somatic and dendr regen events...</p>
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2) branch spike prevalence varies within a cell's place field
from traversal (of the maze) to traversal.</p>
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3) avg branch spike preval varies widely across place cells...</p>
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4) the prevalence of branch spiking predicts the precision and stability of place fields.</p>
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shows histogram...</p>
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shows that v sharp, distinct place field is accomp by v precise high average branch spike prevaence.</p>
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and vice versa.</p>
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see sheffield and Dombeck in 2015 in Nature (get this!)</p>
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and now to stability....
compare day 1 and day 2...</p>
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yes... same finding... those cell switch high avg branch spike precision
are more reproducible over day 1 to day 2.</p>
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(as opposed to somatic place field firing... which is NOT as predicitve )</p>
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now... on to their conceptual model....</p>
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regenerative events in dendrities... (poss windows for plasticity... BUT
doesn't contradict the notion of incr stability due to more regen events in the dendrities)</p>
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how do precise and stable place fields develop?usual mode</p>
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mouse traverse maze</p>
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and multiple CA3 place fields fire and converge onto a single CA1 place cell which fires at that place (due to multiple inputs from the CA3 cells...</p>
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so we see lots of CA2 firing of that cells soma at place #1 but not at place #2.</p>
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(usual model)</p>
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and a few traversals later...</p>
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get somatic potentiation to increase the firing at place #1 (of the soma on place field CA1 place cell.</p>
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and many traversals later... due to learning (reinforement, etc) and synaptic connex then
get more distinct and precise place field (due to a + feedback effect)
so its gets more precise and more stable...</p>
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as in McHugh 96 and Barry Burgess in 2007...</p>
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similarly for the weak cells that aren't espec correlated... their connex just fade away</p>
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*</p>
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testing modes predictions...</p>
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</p>
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summary:</p>
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1) regenerative events occur in place dell dendrites during place field firing</p>
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2) branch spiking is hihgly spatiotemp variable from place field to place field and across trversal/</p>
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we propose that branch spike to lead to place field learning.</p>
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* new topic new project</p>
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DOPAMIC SIGNALING</p>
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in the midbrain...</p>
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SNC subst nigra pars compacta SMc and also the
VTA ventral tegm area. in midbrain but
both project to the STRIATUM...</p>
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post doc convinced his to go to SNC (since its well know)</p>
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straitum... habit learning, reqrde based mtor learning... etc.</p>
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when neurons in SNc die... cannot start mvmts (as in Parkinsons)</p>
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Schultz and Romo in 1990 would reward signaling in monkeys....
had to reach up into box to get food pellet..</p>
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see single unit record and EMG (when arm begining to do the reach)</p>
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they see burst when monkey finds food peller in the box...</p>
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reward prediciton error signal... DA is involved (and also in learning movement ...</p>
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when at rest DA neurons jsut slowing ticking away... perhhaps "mvmt permssive"</p>
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when unexpected reward +> get phasic DA burst due to unpredicted reward (as oppose dto the slow tonic release)</p>
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expt: label SNc/ VTA neuros wit AAV1-folex GCAMO6f...</p>
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put 2PM over striatum of mouse.</p>
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see many neurons coming into stratum (a tangled web of axons coming from midbrain...
indicating the tonic release of DA. (random spikng)</p>
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but then he'd give reward to mice and got no change... WT hell???</p>
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but did see a few axons they worked as expected (lit up with rewards)</p>
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so is the phasic signaling due to? answer is locomotionl</p>
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mice run a lot... they are time-locked to the accel on the Tank treadmill.</p>
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<b>fast phasic motor signal causes DA release in SNc and VTA... </b>
seems purely motor related (surprise!)</p>
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but is this just correlational or causal in relation to movement?</p>
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next stim stiatum iwth blue lase after AAV-floxed CHR2 yfp.</p>
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<b>DA signaling can drive locomotion </b>and can entrain locomotion frequency...</p>
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we can cause mvmt.</p>
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<b>seems that phasic DA signaling can drive motion</b>.</p>
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dorsal straitum... gets motor signaling</p>
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and vetnral striatum only... has reward signalling...</p>
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fast phasic DA signaling locked to accel in the DORSAL striatum...</p>
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the reward signaling seems to the in VENTRAL striatum...</p>
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there is a gradient from (top tob ottom... from dorsum to ventral sruface)</p>
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Q... and answer... lack of DA in dorsal stra. seems to predict whether the dynamic will STOP ...</p>
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