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Marrero, K.

Publications and source records attributed to Marrero, K..

4 recordsLinked to original sources

Cellular and circuit features distinguish dentate gyrus semilunar granule cells and granule cells activated during contextual memory formation

The dentate gyrus is critical for spatial memory formation and shows task related activation of cellular ensembles considered as memory engrams. Semilunar granule cells (SGCs), a sparse dentate projection neuron subtype distinct from granule cells (GCs), were recently reported to be enriched among behaviorally activated neurons. However, the mechanisms governing SGC recruitment during memory formation and their role in engram refinement remains unresolved. By examining neurons labeled during contextual memory formation in TRAP2 mice, we empirically tested competing hypotheses for GC and SGC recruitment into memory ensembles. In support of the proposal that more excitable neurons are preferentially recruited into memory ensembles, SGCs showed greater sustained firing than GCs. Additionally, SGCs labeled during memory formation showed less adapting firing than unlabeled SGCs. Our recordings did not reveal glutamatergic connections between behaviorally labeled SGCs and GCs, providing evidence against SGC driven local circuit feedforward excitation in ensemble recruitment. Contrary to a leading hypothesis, there was little evidence for individual SGCs or labeled neuronal ensembles supporting lateral inhibition of unlabeled neurons. Instead, labeled GCs and SGCs received more spontaneous excitatory synaptic inputs than their unlabeled counterparts. Moreover, pairs of GCs and SGCs within labeled neuronal cohorts received more temporally correlated spontaneous excitatory synaptic inputs than labeled-unlabeled neuronal pairs, validating a role for correlated afferent inputs in neuronal ensemble selection. These findings challenge the proposal that SGCs drive dentate GC ensemble refinement, while supporting a role for intrinsic active properties and correlated inputs in preferential SGC recruitment to contextual memory engrams. Impact StatementEvaluation of semilunar granule cell involvement in dentate gyrus contextual memory processing supports recruitment based on intrinsic and input characteristics while revealing limited contribution to ensemble refinement. Major subject area, keywords and organismsSemilunar granule cell, inhibition, memory, engram, circuit, hippocampus

neuroscience↗

Multiple Temporal and Object-Based Strategies Across Learning for a Selective Detection Task in Mice

New tasks are often learned in stages with each stage reflecting a different learning challenge. Accordingly, each learning stage is likely mediated by distinct neuronal processes. And yet, most rodent studies of the neuronal correlates of goal-directed learning focus on individual outcome measures and individual brain regions. Here, we longitudinally studied mice from naive to expert performance in a head-fixed, operant conditioning whisker discrimination task. In addition to tracking the primary behavioral outcome of stimulus discrimination, we tracked and compared an array of object-based and temporal-based behavioral measures. These behavioral analyses identify multiple, partially overlapping learning stages in this task, consistent with initial response implementation, early stimulus-response generalization, and late response inhibition. To begin to understand the neuronal foundations of these learning processes, we performed widefield Ca2+ imaging of dorsal neocortex throughout learning and correlated behavioral measures with neuronal activity. We found distinct and widespread correlations between neocortical activation patterns and various behavioral measures. For example, improvements in sensory discrimination correlated with target stimulus evoked activations of licking-related cortices along with distractor stimulus evoked global cortical suppression. Our study reveals multidimensional learning for a simple goal-directed learning task and generates hypotheses for the neuronal modulations underlying these various learning processes.

animal behavior and cognition↗

Global, Low Amplitude Cortical State Predicts Response Outcomes in a Selective Detection Task

Spontaneous neuronal activity strongly impacts stimulus encoding and behavioral responses. We sought to determine the effects of neocortical prestimulus activity on stimulus detection. We trained mice in a selective whisker detection task, in which they learned to respond (lick) to target stimuli in one whisker field and ignore distractor stimuli in the contralateral whisker field. During expert task performance, we used widefield Ca2+ imaging to assess prestimulus and post-stimulus neuronal activity broadly across frontal and parietal cortices. We found that lower prestimulus activity correlated with enhanced stimulus detection: lower prestimulus activity predicted response versus no response outcomes and faster reaction times. The activity predictive of trial outcome was distributed through dorsal neocortex, rather than being restricted to whisker or licking regions. Using principal component analysis, we demonstrate that response trials are associated with a distinct and less variable prestimulus neuronal subspace. For single units, prestimulus choice probability was weak yet distributed broadly, with lower than chance choice probability correlating with stronger sensory and motor encoding. These findings support a low amplitude, low variability, optimal prestimulus cortical state for stimulus detection that presents globally and predicts response outcomes for both target and distractor stimuli.

neuroscience↗

Functional Localization of an Attenuating Filter within Cortex for a Selective Detection Task in Mice

An essential feature of goal-directed behavior is the ability to selectively respond to the diverse stimuli in ones environment. However, the neural mechanisms that enable us to respond to target stimuli while ignoring distractor stimuli are poorly understood. To study this sensory selection process, we trained male and female mice in a selective detection task in which mice learn to respond to rapid stimuli in the target whisker field and ignore identical stimuli in the opposite, distractor whisker field. In expert mice, we used widefield Ca2+ imaging to analyze target-related and distractor-related neural responses throughout dorsal cortex. For target stimuli, we observed strong signal activation in primary somatosensory cortex (S1) and frontal cortices, including both the whisker representation of primary motor cortex (wMC) and anterior lateral motor cortex (ALM). For distractor stimuli, we observe strong signal activation in S1, with minimal propagation to frontal cortex. Our data support only modest subcortical filtering, with robust, step-like attenuation in distractor processing between mono-synaptically coupled regions of S1 and wMC. This study establishes a highly robust model system for studying the neural mechanisms of sensory selection and places important constraints on its implementation. SummaryResponding to task-relevant stimuli while ignoring task-irrelevant stimuli is critical for goal-directed behavior. Yet, the neural mechanisms involved in this selection process are poorly understood. We trained mice in a detection task with both target and distractor stimuli. During expert performance, we measured neural activity throughout cortex using widefield imaging. We observed responses to target stimuli in multiple sensory and motor cortical regions. In contrast, responses to distractor stimuli were abruptly suppressed beyond sensory cortex. Our findings localize the sites of attenuation when successfully ignoring a distractor stimulus, and provide essential foundations for further revealing the neural mechanism of sensory selection and distractor suppression.

neuroscience↗