Experience-dependent reorganization of inhibitory neuron synaptic connectivity.

Organisms continually tune their perceptual systems to the features they encounter in their environment. 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 , training a deep convolutional network to reliably identify monosynaptic connections from the spike-time cross-correlograms of 4.

Representations of the intrinsic value of information in mouse orbitofrontal cortex.

Animals are motivated to seek information that does not influence reward outcomes, suggesting that information has intrinsic value. We have developed an odor-based information seeking task that reveals that mice choose to receive information even though it does not alter the reward outcome. Moreover, mice are willing to pay for information by sacrificing water reward, suggesting that information is of intrinsic value to a mouse.

Phased nanopore assembly with Shasta and modular graph phasing with GFAse.

Reference-free genome phasing is vital for understanding allele inheritance and the impact of single-molecule DNA variation on phenotypes. To achieve thorough phasing across homozygous or repetitive regions of the genome, long-read sequencing technologies are often used to perform phased de novo assembly. As a step toward reducing the cost and complexity of this type of analysis, we describe new methods for accurately phasing Oxford Nanopore Technologies (ONT) sequence data with the Shasta genome assembler and a modular tool for extending phasing to the chromosome scale called GFAse.

A brain atlas for the camouflaging dwarf cuttlefish, Sepia bandensis.

The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied marine mollusks that exhibit an array of interesting biological phenomena, including dynamic camouflage, complex social behaviors, prehensile regenerating arms, and large brains capable of learning, memory, and problem-solving. The dwarf cuttlefish, Sepia bandensis, is a promising model cephalopod species due to its small size, substantial egg production, short generation time, and dynamic social and camouflage behaviors. Cuttlefish dynamically camouflage to their surroundings by changing the color, pattern, and texture of their skin.

A rapid and bidirectional reporter of neural activity reveals neural correlates of social behaviors in Drosophila.

Neural activity is modulated over different timescales encompassing subseconds to hours, reflecting changes in external environment, internal state and behavior. Using Drosophila as a model, we developed a rapid and bidirectional reporter that provides a cellular readout of recent neural activity. This reporter uses nuclear versus cytoplasmic distribution of CREB-regulated transcriptional co-activator (CRTC).

Flexible neural control of transition points within the egg-laying behavioral sequence in Drosophila.

Innate behaviors are frequently comprised of ordered sequences of component actions that progress to satisfy essential drives. Progression is governed by specialized sensory cues that induce transitions between components within the appropriate context. Here we have characterized the structure of the egg-laying behavioral sequence in Drosophila and found significant variability in the transitions between component actions that affords the organism an adaptive flexibility.

Phased nanopore assembly with Shasta and modular graph phasing with GFAse.

As a step towards simplifying and reducing the cost of haplotype resolved assembly, we describe new methods for accurately phasing nanopore data with the Shasta genome assembler and a modular tool for extending phasing to the chromosome scale called GFAse. We test using new variants of Oxford Nanopore Technologies' (ONT) PromethION sequencing, including those using proximity ligation and show that newer, higher accuracy ONT reads substantially improve assembly quality.

Individual bitter-sensing neurons in Drosophila exhibit both ON and OFF responses that influence synaptic plasticity.

The brain generates internal representations that translate sensory stimuli into appropriate behavior. In the taste system, different tastes activate distinct populations of sensory neurons. We investigated the temporal properties of taste responses in Drosophila and discovered that different types of taste sensory neurons show striking differences in their response dynamics.

Olfactory landmarks and path integration converge to form a cognitive spatial map.

The convergence of internal path integration and external sensory landmarks generates a cognitive spatial map in the hippocampus. We studied how localized odor cues are recognized as landmarks by recording the activity of neurons in CA1 during a virtual navigation task. We found that odor cues enriched place cell representations, dramatically improving navigation.

Evolving the olfactory system with machine learning.

The convergent evolution of the fly and mouse olfactory system led us to ask whether the anatomic connectivity and functional logic of olfactory circuits would evolve in artificial neural networks trained to perform olfactory tasks. Artificial networks trained to classify odor identity recapitulate the connectivity inherent in the olfactory system. Input units are driven by a single receptor type, and units driven by the same receptor converge to form a glomerulus.

Representational drift in primary olfactory cortex.

Perceptual constancy requires the brain to maintain a stable representation of sensory input. In the olfactory system, activity in primary olfactory cortex (piriform cortex) is thought to determine odour identity. Here we present the results of electrophysiological recordings of single units maintained over weeks to examine the stability of odour-evoked responses in mouse piriform cortex.

Embryonic development of the camouflaging dwarf cuttlefish, Sepia bandensis.

Background: The dwarf cuttlefish Sepia bandensis, a camouflaging cephalopod from the Indo-Pacific, is a promising new model organism for neuroscience, developmental biology, and evolutionary studies. Cuttlefish dynamically camouflage to their surroundings by altering the color, pattern, and texture of their skin. The skin's "pixels" (chromatophores) are controlled by motor neurons projecting from the brain.

Synaptic Organization of Anterior Olfactory Nucleus Inputs to Piriform Cortex.

Odors activate distributed ensembles of neurons within the piriform cortex, forming cortical representations of odor thought to be essential to olfactory learning and behaviors. This odor response is driven by direct input from the olfactory bulb, but is also shaped by a dense network of associative or intracortical inputs to piriform, which may enhance or constrain the cortical odor representation. With optogenetic techniques, it is possible to functionally isolate defined inputs to piriform cortex and assess their potential to activate or inhibit piriform pyramidal neurons.

Transient and Persistent Representations of Odor Value in Prefrontal Cortex.

The representation of odor in olfactory cortex (piriform) is distributive and unstructured and can only be afforded behavioral significance upon learning. We performed 2-photon imaging to examine the representation of odors in piriform and in two downstream areas, the orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC), as mice learned olfactory associations. In piriform, we observed that odor responses were largely unchanged during learning.

Context-Dependent Decision Making in a Premotor Circuit.

Cognitive capacities afford contingent associations between sensory information and behavioral responses. We studied this problem using an olfactory delayed match to sample task whereby a sample odor specifies the association between a subsequent test odor and rewarding action. Multi-neuron recordings revealed representations of the sample and test odors in olfactory sensory and association cortex, which were sufficient to identify the test odor as match or non-match.

The pheromone darcin drives a circuit for innate and reinforced behaviours.

Organisms have evolved diverse behavioural strategies that enhance the likelihood of encountering and assessing mates. Many species use pheromones to communicate information about the location, sexual and social status of potential partners. In mice, the major urinary protein darcin-which is present in the urine of males-provides a component of a scent mark that elicits approach by females and drives learning.

Acetic acid activates distinct taste pathways in to elicit opposing, state-dependent feeding responses.

Taste circuits are genetically determined to elicit an innate appetitive or aversive response, ensuring that animals consume nutritious foods and avoid the ingestion of toxins. We have examined the response of to acetic acid, a tastant that can be a metabolic resource but can also be toxic to the fly. Our data reveal that flies accommodate these conflicting attributes of acetic acid by virtue of a hunger-dependent switch in their behavioral response to this stimulus.

A virtual burrow assay for head-fixed mice measures habituation, discrimination, exploration and avoidance without training.

We have designed an assay that measures approach and avoidance behaviors in head-fixed mice at millisecond timescale, is compatible with standard electrophysiological and optical methods for measuring neuronal activity, and requires no training. The Virtual Burrow Assay simulates a scenario in which a mouse, poised at the threshold of its burrow, evaluates whether to exit the enclosure or to retreat inside. The assay provides a sensitive readout of habituation, discrimination and exploration, as well as avoidance of both conditioned and innately aversive cues.

Odor Perception on the Two Sides of the Brain: Consistency Despite Randomness.

Neurons in piriform cortex receive input from a random collection of glomeruli, resulting in odor representations that lack the stereotypic organization of the olfactory bulb. We have performed in vivo optical imaging and mathematical modeling to demonstrate that correlations are retained in the transformation from bulb to piriform cortex, a feature essential for generalization across odors. Random connectivity also implies that the piriform representation of a given odor will differ among different individuals and across brain hemispheres in a single individual.

Representations of Novelty and Familiarity in a Mushroom Body Compartment.

Animals exhibit a behavioral response to novel sensory stimuli about which they have no prior knowledge. We have examined the neural and behavioral correlates of novelty and familiarity in the olfactory system of Drosophila. Novel odors elicit strong activity in output neurons (MBONs) of the α'3 compartment of the mushroom body that is rapidly suppressed upon repeated exposure to the same odor.

Optimal Degrees of Synaptic Connectivity.

Synaptic connectivity varies widely across neuronal types. Cerebellar granule cells receive five orders of magnitude fewer inputs than the Purkinje cells they innervate, and cerebellum-like circuits, including the insect mushroom body, also exhibit large divergences in connectivity. In contrast, the number of inputs per neuron in cerebral cortex is more uniform and large.

Neural Representations of Unconditioned Stimuli in Basolateral Amygdala Mediate Innate and Learned Responses.

Stimuli that possess inherently rewarding or aversive qualities elicit emotional responses and also induce learning by imparting valence upon neutral sensory cues. Evidence has accumulated implicating the amygdala as a critical structure in mediating these processes. We have developed a genetic strategy to identify the representations of rewarding and aversive unconditioned stimuli (USs) in the basolateral amygdala (BLA) and have examined their role in innate and learned responses.

The neuronal architecture of the mushroom body provides a logic for associative learning.

We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes.

The participation of cortical amygdala in innate, odour-driven behaviour.

Innate behaviours are observed in naive animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centres have been anatomically defined, but the specific pathways responsible for innate responses to volatile odours have not been identified. Here we devise genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviours.