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Abstracts - Association for Chemoreception Sciences

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#35 SYMPOSIUM:<br />

NEW APPROACHES TO PHYSIOLOGY<br />

AND BEHAVIOR IN AWAKE RODENTS<br />

Dramatic state-dependency of the activity of granule cells in<br />

the mouse main olfactory bulb<br />

Stephen D Shea, Brittany N Cazakoff, Kerensa L Crump, Billy Y Lau<br />

Cold Spring Harbor Laboratory Cold Spring Harbor, NY, USA<br />

It is becoming increasingly clear that olfactory representations in<br />

the main olfactory bulb (MOB) are substantially re<strong>for</strong>matted in<br />

awake rodents. In addition to elevated rates and altered temporal<br />

structure in the spike discharge of mitral/tufted cells (MT),<br />

the wakeful state is marked by a fusion of sensory input-driven<br />

responses with activity that reflects attention, experience, and<br />

behavioral task contingencies. It seems likely that as a key target<br />

of many neuromodulatory systems and corticofugal feedback<br />

pathways, the extensive network of inhibitory MOB granule<br />

cells (GC) is instrumental in the state-dependent sculpting of<br />

MT activity patterns. Despite this predicted critical role, few<br />

published studies have demonstrably made electrophysiological<br />

recordings from these small cells. Moreover, none have been<br />

reported in awake animals. As a first step towards closing this<br />

gap, we recently developed reliable methods <strong>for</strong> recording and<br />

labeling GC in awake, head-fixed mice. Our preparation allows<br />

us to directly compare the activity and sensory responses of<br />

the same GC during wakefulness and inhalant anesthesia.<br />

Our data reveal that GC in awake mice are dramatically more<br />

spontaneously active, and exhibit stronger, more broadly-tuned<br />

sensory responses that include both increases and decreases<br />

in spike rate. Under either of two pharmacologically-distinct<br />

anesthetics, many of these cells emit very few spontaneous<br />

or stimulus-driven spikes. Those that have somewhat higher<br />

spontaneous rates still exhibit little response to odors. We are<br />

currently quantifying the variable respiratory coupling of GC in<br />

awake animals, and assessing the effects of stimulus novelty or<br />

familiarity on GC odor responses.<br />

#36 SYMPOSIUM:<br />

NEW APPROACHES TO PHYSIOLOGY<br />

AND BEHAVIOR IN AWAKE RODENTS<br />

Response properties of cortico-bulbar feedback and granule<br />

cells in awake head-fixed mice<br />

Dinu F Albeanu, Hong goo Chae, Gonzalo H Otazu<br />

Cold Spring Harbor Laboratory Cold Spring Harbor, NY, USA<br />

Sensory circuits integrate inputs from the environment, as well<br />

as feedback signals from higher brain regions, in a close loop<br />

manner. The interplay of feed-<strong>for</strong>ward and feedback signals<br />

has been proposed to be fundamental <strong>for</strong> learning and memory<br />

recall. Though rich cortical feedback projections innervate<br />

the mouse olfactory bulb, to date, little is known about their<br />

contribution to olfactory processing. Cortico-bulbar feedback<br />

primarily targets the granule cells (GC), which <strong>for</strong>m extensive<br />

dendro-dendritic synapses with the mitral/tufted cells. To<br />

examine how cortical feedback shapes processing in the bulb,<br />

we used genetically encoded calcium indicators (GCaMP3&5)<br />

and multiphoton imaging to monitor the odor evoked responses<br />

of feedback fibers and granule cells, in awake head-fixed mice.<br />

GCs and feedback fibers showed rich spontaneous activity and<br />

diverse excitatory and inhibitory odor responses. On average,<br />

to our stimulus panel (up to 30 odors), we observed 54% purely<br />

excitatory and only 17% purely inhibitory responses in the<br />

GCs, while the two response types were equally common in<br />

the feedback fibers. Interestingly, both GCs and feedback fibers,<br />

that showed spontaneous activity, were inhibited upon odor<br />

presentation, irrespective of stimulus identity. While inhibition<br />

of feedback fibers was sparse and odor specific, GCs showed<br />

both broad, and narrowly tuned inhibitory responses. Further,<br />

a significant fraction (~25%) of GCs exhibited excitatory OFF<br />

responses, independent of stimulus duration. We are currently<br />

investigating how response properties of GCs and feedback<br />

fibers are shaped by odor experience and during rein<strong>for</strong>cement<br />

learning. Additionally, we are employing pharmacological and<br />

optogenetic approaches to modulate the feedback fibers, while<br />

simultaneously monitoring granule cell activity.<br />

#37 SYMPOSIUM:<br />

NEW APPROACHES TO PHYSIOLOGY<br />

AND BEHAVIOR IN AWAKE RODENTS<br />

Odor-guided behaviors in head-restrained and<br />

freely-moving mice<br />

Venkatesh N Murthy 1,2 , Dan Rokni 1,2 , David H. Gire 1,2 ,<br />

Daniel Millman 1,2<br />

1<br />

Harvard University, Molecular & Cellular Biology Cambridge,<br />

MA, USA, 2 Harvard University, Center <strong>for</strong> Brain Science Cambridge,<br />

MA, USA<br />

Olfaction plays a central role in guiding behavior in many<br />

animals, including the common laboratory mammalian models<br />

– rats and mice. There is a renewed excitement about studying<br />

the neural basis of such behaviors, which entails developing<br />

behavioral tasks under controlled conditions where neural<br />

activity can be recorded and manipulated. We have trained mice<br />

to per<strong>for</strong>m odor tasks while their heads are restrained, which<br />

allows stable electrophysiological recordings, high-resolution<br />

optical imaging and optogenetic manipulation. In one such task,<br />

head-restrained mice can be trained to recognize target odorants<br />

embedded in unpredictable and variable background mixtures.<br />

We have also developed strategies to study odor-guided behaviors<br />

in freely moving animals, including spatial navigation. We will<br />

present a detailed analysis of these behaviors in our talk, and<br />

some initial ef<strong>for</strong>ts in recording and imaging neural activity<br />

under these conditions. Acknowledgements: R01DC011291<br />

ORAL ABSTRACTS<br />

<strong>Abstracts</strong> are printed as submitted by the author(s).<br />

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