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Fink, A. J. P.

Publications and source records attributed to Fink, A. J. P..

5 recordsLinked to original sources

Experience-dependent reorganization of inhibitory neuron synaptic connectivity

Organisms continually tune their perceptual systems to the features they encounter in their environment1-3. We have studied how ongoing experience reorganizes the synaptic connectivity of neurons in the olfactory (piriform) cortex of the mouse. We developed an approach to measure synaptic connectivity in vivo, training a deep convolutional network to reliably identify monosynaptic connections from the spike-time cross-correlograms of 4.4 million single-unit pairs. This revealed that excitatory piriform neurons with similar odor tuning are more likely to be connected. We asked whether experience enhances this like-to-like connectivity but found that it was unaffected by odor exposure. Experience did, however, alter the logic of interneuron connectivity. Following repeated encounters with a set of odorants, inhibitory neurons that responded differentially to these stimuli exhibited a high degree of both incoming and outgoing synaptic connections within the cortical network. This reorganization depended only on the odor tuning of the inhibitory interneuron and not on the tuning of its pre- or postsynaptic partners. A computational model of this reorganized connectivity predicts that it increases the dimensionality of the entire networks responses to familiar stimuli, thereby enhancing their discriminability. We confirmed that this network-level property is present in physiological measurements, which showed increased dimensionality and separability of the evoked responses to familiar versus novel odorants. Thus, a simple, non-Hebbian reorganization of interneuron connectivity may selectively enhance an organisms discrimination of the features of its environment.

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The representational geometry of emotional states in basolateral amygdala

Sensory stimuli associated with aversive outcomes cause multiple behavioral responses related to an animals evolving emotional state, but neural mechanisms underlying these processes remain unclear. Here aversive stimuli were presented to mice, eliciting two responses reflecting fear and flight to safety: tremble and ingress into a virtual burrow. Inactivation of basolateral amygdala (BLA) eliminated differential responses to aversive and neutral stimuli without eliminating responses themselves, suggesting BLA signals valence, not motor commands. However, two-photon imaging revealed that neurons typically exhibited mixed selectivity for stimulus identity, valence, tremble and/or ingress. Despite heterogeneous selectivity, BLA representational geometry was lower-dimensional when encoding valence, tremble and safety, enabling generalization of emotions across conditions. Further, tremble and valence coding directions were orthogonal, allowing linear readouts to specialize. Thus BLA representational geometry confers two computational properties that identify specialized neural circuits encoding variables describing emotional states: generalization across conditions, and readouts lacking interference from other readouts.

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Sensory experience steers representational drift in mouse visual cortex

Representational drift - the gradual continuous change of neuronal representations - has been observed across many brain areas. It is unclear whether drift is caused by synaptic plasticity elicited by sensory experience, or by the intrinsic volatility of synapses. Here, using chronic two-photon calcium imaging in mouse primary visual cortex, we find that the preferred stimulus orientation of individual neurons slowly drifts over the course of weeks. By using cylinder lens goggles to limit visual experience to a narrow range of orientations, we show that the direction of drift, but not its magnitude, is biased by the statistics of visual input. A network model suggests that drift of preferred orientation largely results from synaptic volatility, which under normal visual conditions is counteracted by experience-driven Hebbian mechanisms, stabilizing preferred orientation. Under deprivation conditions these Hebbian mechanisms enable adaptation. Thus, Hebbian synaptic plasticity steers drift to match the statistics of the environment.

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Representational drift in primary olfactory cortex

Representations of the external world in sensory cortices may define the identity of a stimulus and should therefore vary little over the life of the organism. In the olfactory system the primary olfactory cortex, piriform, is thought to determine odor identity1-6. We have performed electrophysiological recordings of single units maintained over weeks to examine the stability of odor representations in the mouse piriform cortex. We observed that odor representations drift over time, such that the performance of a linear classifier trained on the first recording day approaches chance levels after 32 days. Daily exposure to the same odorant slows the rate of drift, but when exposure is halted that rate increases once again. Moreover, behavioral salience does not stabilize odor representations. Continuous drift poses the question of the role of piriform in odor identification. This instability may reflect the unstructured connectivity of piriform7-15 and may be a property of other unstructured cortices.

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A naturalistic assay for measuring behavioral responses to aversive stimuli at millisecond timescale

We have designed a Virtual Burrow Assay (VBA) to detect the behavioral responses of head-fixed mice to aversive stimuli. We demonstrate its suitability for measuring novelty detection as well as aversion to both conditioned and innately aversive cues. The VBA simulates a scenario in which a mouse, poised at the threshold of its burrow, evaluates whether to remain exposed to potential threats outside or to retreat inside an enclosure. When presented with aversive stimuli, mice exhibit a stereotyped retreat whose onset is determined by measuring the position of a moveable burrow. This withdrawal, which requires no training, is characterized by an abrupt transition that unfolds within milliseconds--a timescale similar to that of neuronal dynamics, permitting direct comparison between the two. The assay is compatible with standard electrophysiological and optical methods for measuring and perturbing neuronal activity.

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