Andrew Fink, Ph.D. and Carl Schoonover, Ph.D.
Department of Neuroscience
Columbia University / Howard Hughes Medical Institute

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ABSTRACT
We have discovered that in the rodent primary olfactory cortex (piriform) the pattern of neural activity evoked by a smell changes with the passage of time. These changes, which unfold absent a task or learning paradigm, accumulate to such an extent that after just a few weeks odor responses bear little resemblance to their original form. The piriform has been traditionally hypothesized to establish the identity of odorants. Our observations have forced us to radically reconsider the role of this vast brain region in olfactory perception. We propose that the piriform operates instead as a flexible learning system, a ‘scratch pad’ that continually learns and continually overwrites itself. This poses the problem of how transient memory traces can subsequently be stored over long timescales.

These results also raise the question of what the piriform learns. We have designed a behavioral assay that provides a sensitive readout of whether mice expect a given sensory event. Using this assay we have demonstrated that mice learn the identity, order and precise timing of elements in a sequence of neutral odorants, A-->B, without reward or punishment. Simultaneous recordings in naïve piriform show strong and distinct responses to both A and B. These diminish with experience in a manner that tracks these expectations: predictable cues, such as B in the A-->B sequence, evoke hardly any response in experienced animals. This does not reflect simple adaptation. When B is presented alone, it elicits robust activation. When B is omitted, and A is presented alone, piriform exhibits vigorous activity at the precise moment when the animal, expecting odor B, encounters nothing. Thus, when the external world conforms to expectation, piriform is relatively quiescent, but any departure from the expected results in vigorous activation. We hypothesize that the piriform learns to implement a comparator that reports the difference between the world as it expects it and the world as it is. The biological learning mechanisms that generate this predictive activity, a feature more commonly encountered in higher order cortices, can be readily studied and probed in a circuit only two synapses from the sensory periphery.

SPEAKER BIOS
We are postdoctoral fellows in Richard Axel’s laboratory at Columbia University, where we carry out a shared research program. We seek to understand how organisms learn continuously while also storing stable memories over their lifetimes. The rodent olfactory system, an easily accessible, well-defined circuit whose input can be precisely controlled, presents a relatively simple and tractable model to address these basic open problems. We have established methods for long-term observation of neurophysiological activity in the rodent primary olfactory cortex (piriform), and developed naturalistic ethological behavioral paradigms to probe continuous learning.

As graduate students, Carl Schoonover (BA Philosophy, Harvard College) studied the thalamocortical projection to primary somatosensory cortex under the supervision of Dr. Randy Bruno, and Andrew Fink (BA Physics, Carleton College) studied spinal presynaptic inhibition under the supervision of Dr. Thomas Jessell. 

Host: Dr. Tim Cope