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Hawk, J. D.

Publications and source records attributed to Hawk, J. D..

6 recordsLinked to original sources

Experience-Dependent Gain Modulation Drives Thermosensory Responses in Behavior

Sensory neurons must extract behaviorally relevant features from dynamic environments while maintaining sensitivity across wide stimulus ranges. To understand how sensory encoding adapts to experience during behavior, we combine long-duration calcium imaging in freely moving C. elegans with a temperature-trajectory playback paradigm to determine how the thermosensory neuron AFD extracts behaviorally relevant sensory features during navigation. We observe that AFD functions as a leaky integrator of recently experienced temperature changes, accumulating thermal inputs over a rolling window of tens of seconds, resulting in calcium levels that represent recent temperature dynamics during runs. Importantly, we determine that AFD selectively amplifies responses to temperature changes near its learned preferred temperature. This experience-dependent gain control aligns encoding with the navigational goal, providing a mechanism for representing temperature preference within a derivative-based sensory system. A minimal mathematical model incorporating derivative detection, leaky integration, and temperature-dependent gain captures the calcium dynamics over a range of stimuli, and a simulation based on the mathematical model predicts goal-oriented locomotor strategies across stimulus regimes. Together, these findings show how gain control allows a derivative-based sensory code to represent an absolute goal and guide locomotory strategies during navigation. HighlightsO_LIAFD encodes recent temperature changes over behaviorally relevant timescales. C_LIO_LIAFD amplifies temperature-change responses within a learned temperature-centered gain window. C_LIO_LIGain control provides a mechanism for representing distance to temperature preference within the derivative-based sensory system. C_LIO_LIA mathematical model and simulation of derivative sensing, leaky integration, and gain control predicts AFD calcium responses and goal-oriented locomotory strategies across stimulus regimes. C_LI

neuroscience↗

Specific configurations of electrical synapses filter sensory information to drive choices in behavior

Synaptic configurations in precisely wired circuits underpin how sensory information is processed by the nervous system, and the emerging animal behavior. This is best understood for chemical synapses, but far less is known about how electrical synaptic configurations modulate, in vivo and in specific neurons, sensory information processing and context-specific behaviors. We discovered that INX-1, a gap junction protein that forms electrical synapses, is required to deploy context-specific behavioral strategies during C. elegans thermotaxis behavior. INX-1 couples two bilaterally symmetric interneurons, and this configuration is required for the integration of sensory information during migration of animals across temperature gradients. In inx-1 mutants, uncoupled interneurons display increased excitability and responses to subthreshold temperature stimuli, resulting in abnormally longer run durations and context-irrelevant tracking of isotherms. Our study uncovers a conserved configuration of electrical synapses that, by increasing neuronal capacitance, enables differential processing of sensory information and the deployment of context-specific behavioral strategies. One-Sentence SummaryCoupling of interneurons by electrical synapses reduces membrane resistance and filters sensory inputs to guide sensory-dependent behavioral choices.

neuroscience↗

The CBP KIX domain regulates long-term memory and circadian activity

CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors. Identifying specific domain functions for multi-action proteins is essential to understand processes necessary for healthy living including cognitive function and a robust circadian clock. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. We found that CBPKIX/KIX mice were impaired in long-term, but not short-term spatial memory in the Morris water maze. Using an unbiased analysis of gene expression after training for hippocampus-dependent memory, we discovered dysregulation of CREB and CLOCK target genes and downregulation of circadian genes in CBPKIX/KIX mice. With our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark, although phase resetting to light was comparable to wildtype. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.

neuroscience↗

HySyn: A genetically-encoded synthetic synapse to rewire neural circuits in vivo

Here we introduce HySyn, a system designed to rewire neural connectivity in vivo by reconstituting a functional heterologous synapse. We demonstrate that genetically targeted expression of the two HySyn components, a Hydra-derived neuropeptide and its receptor, creates de novo neuromodulatory transmission in a mammalian neuronal tissue culture model and rewires a behavioral circuit in vivo in the nematode Caenorhabditis elegans. HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or modulate specific neural circuits.

neuroscience↗

Automated analysis of sleep in adult C. elegans with closed-loop assessment of state-dependent neural activity

Sleep, a state of quiescence associated with growth and restorative processes, is conserved across species. Invertebrates including the nematode Caenorhabditis elegans exhibit sleep-like states during development and periods of satiety and stress. Here we describe two methods to study behavior and associated neural activity during sleep and awake states in adult C. elegans. A large microfluidic device facilitates population-wide assessment of long-term sleep behavior over 12 h, including effects of fluid flow, oxygen, feeding, odors, and genetic perturbations. Smaller devices allow simultaneous recording of sleep behavior and neuronal activity, and a closed-loop sleep detection system delivers chemical stimuli to individual animals to assess sleep-dependent changes to neural responses. Sleep increased the arousal threshold to aversive chemical stimulation, yet sensory neuron (ASH) and first-layer interneuron (AIB) responses were unchanged. This localizes adult sleep-dependent neuromodulation within interneurons presynaptic to the AVA premotor interneurons, rather than afferent sensory circuits.

neuroscience↗

Integration of plasticity mechanisms within a single sensory neuron of C. elegans actuates a memory

Neural plasticity--the ability of a neuron to change its cellular properties in response to past experiences--underpins the nervous systems capacity to form memories and actuate behaviors. How different plasticity mechanisms act together in vivo and at a cellular level to transform sensory information into behavior is not well understood. Here we show that in the nematode C. elegans two plasticity mechanisms--sensory adaptation and presynaptic plasticity--act within a single cell to encode thermosensory information and actuate a temperature-preference memory. Sensory adaptation enables the primary thermosensory neuron, AFD, to adjust the temperature range of its sensitivity to the local environment, thereby optimizing its ability to detect temperature fluctuations associated with migration. Presynaptic plasticity transforms this thermosensory information into a behavioral preference by gating synaptic communication between sensory neuron AFD and its postsynaptic partner, AIY. The gating of synaptic communication is regulated at AFD presynaptic sites by the conserved kinase nPKC{varepsilon}. Bypassing or altering AFD presynaptic plasticity predictably changes the learned behavioral preferences without affecting sensory responses. Our findings indicate that two distinct and modular neuroplasticity mechanisms function together within a single sensory neuron to encode multiple components of information required to enact thermotactic behavior. The integration of these plasticity mechanisms result in a single-cell logic system that can both represent sensory stimuli and guide memory-based behavioral preference.

neuroscience↗