Biology subjects

Sur, M.

Publications and source records attributed to Sur, M..

6 recordsLinked to original sources

bioRxiv2018

Active control of arousal by a locus coeruleus GABAergic circuit

Arousal and novelty responses linked to locus coeruleus noradrenergic (LC-NA) activity affect cognitive performance. However, the mechanisms that control modes of LC-NA activity remain unknown. Here, we reveal a local population of GABAergic neurons (LC-GABA) capable of modulating LC-NA activity and arousal. Monosynaptic retrograde virus tracing shows that inputs to LC-GABA and LC-NA neurons arise from similar regions, though a few regions provide differential inputs to one subtype over the other. Recordings in the LC demonstrate two modes of LC-GABA responses whereby spiking is either correlated or broadly anti-correlated with LC-NA responses, reflecting anatomically similar and functionally coincident inputs, or differential and non-coincident inputs, to LC-NA and LC-GABA neurons. Coincident inputs control the gain of phasic LC-NA mediated novelty responses, while non-coincident inputs, such as from the prefrontal cortex to LC, alter overall levels of LC-NA responses without affecting response gain. These findings demonstrate distinct modes by which an inhibitory LC circuit regulates the gain and tone of arousal in the brain.

neuroscience↗

bioRxiv2018

Bidirectional control of orienting behavior by distinct prefrontal circuits

Sensorimotor behaviors require processing of behaviorally relevant sensory cues and the ability to select appropriate responses from a vast behavioral repertoire. Top-down modulation by the prefrontal cortex (PFC) is thought to be key for both processes but the precise role of specific circuits remains unclear. We examined the sensorimotor function of anatomically distinct outputs from a subdivision of the mouse PFC, the anterior cingulate cortex (ACC). Using a visually guided two-choice behavioral paradigm with multiple cue-response mappings, we dissociated the sensory and motor response components of sensorimotor control. Projection-specific two-photon calcium imaging and optogenetic manipulations show that ACC outputs to the superior colliculus, a key midbrain structure for response selection, principally coordinate specific motor responses. Importantly, ACC outputs exert top-down control by reducing the innate response bias of the superior colliculus. In contrast, ACC outputs to the visual cortex facilitate sensory processing of visual cues. Our results ascribe motor and sensory roles to ACC projections to the superior colliculus and the visual cortex and demonstrate for the first time a circuit motif for PFC function wherein anatomically non-overlapping output pathways coordinate complementary but distinct aspects of visual sensorimotor behavior.

neuroscience↗

bioRxiv2018

Locally coordinated synaptic plasticity shapes cell-wide plasticity of visual cortex neurons in vivo

Plasticity of cortical responses involves activity-dependent changes at synapses, but the manner in which different forms of synaptic plasticity act together to create functional changes in neuronal responses remains unknown. Here we show that spike-timing induced receptive field plasticity of individual visual cortex neurons in vivo is anchored by increases in synaptic strength of identified spines, and is accompanied by a novel decrease in the strength of adjacent spines on a slower time scale. The locally coordinated potentiation and depression of spines involves prominent AMPA receptor redistribution via targeted expression of the immediate early gene Arc. Similar changes accompany recovery of eye-specific responses following monocular deprivation. These findings demonstrate that Hebbian strengthening of activated synapses and heterosynaptic weakening of adjacent synapses, in dendrites with heterogeneous synaptic inputs, co-operatively orchestrate cell-wide plasticity of functional neuronal responses.\n\nOne Sentence SummaryArc-mediated local synaptic plasticity regulates reorganization of synaptic responses on dendritic stretches to mediate functional plasticity of neuronal responses in vivo.

neuroscience↗

bioRxiv2017

Two-Photon Imaging of Striatum Demonstrates Distinct Functions for Striosomes and Matrix in Reinforcement Learning

Despite the discovery of striosomes several decades ago, technical difficulties have hampered the study of their functions. Here we used 2-photon calcium imaging in neuronal birthdate-labeled Mash1-CreER mice to image simultaneously the activity of striosomal and matrix neurons in vivo. We report that with this method we can visually identify circumscribed zones of neuropil that correspond to striosomes as verified in immunostained sections. We find that striosomal neurons, relative to matrix neurons, preferentially encode reward-predicting cues, and that their activity contains more information about expected outcome. These characteristics emerge during training and further strengthen during overtraining. Both striatal compartments are active similarly after reward delivery, firing at neuron-specific times during or after consummatory licking. Finally, we find that immediate reward history strongly modulates neuronal activation in the next trial, especially in matrix neurons. These results suggest that striosomes and matrix have distinct functions in relation to reinforcement learning.

neuroscience↗

bioRxiv2017

Reliable sensory processing in mouse visual cortex through inhibitory interactions between Somatostatin and Parvalbumin interneurons

Cortical neurons often respond to identical sensory stimuli with large variability. However, under certain conditions, the same neurons can also respond highly reliably. The circuit mechanisms that contribute to this modulation, and their influence on behavior remains unknown. Here we used novel double transgenic mice, dual-wavelength calcium imaging and temporally selective optical perturbation to identify an inhibitory neural circuit in visual cortex that can modulate the reliability of pyramidal neurons to naturalistic visual stimuli. Our results, supported by computational models, suggest that somatostatin interneurons (SST-INs) increase pyramidal neuron reliability by suppressing parvalbumin interneurons (PV-INs) via the inhibitory SST[->]PV circuit. Using a novel movie classification task, we further show that, by reducing variability, activating SST-INs can improve the ability of mice to discriminate between ambiguous stimuli. Together, these findings reveal a novel role of the SST[->]PV circuit in modulating the fidelity of neural coding critical for visual perception.

neuroscience↗

bioRxiv2017

Task-Dependent Representations Of Stimulus And Choice In Mouse Parietal Cortex

The posterior parietal cortex (PPC) has been implicated in perceptual decisions, but whether its role is specific to sensory processing or sensorimotor transformation is not well understood. To distinguish these possibilities, we trained mice of either sex to perform a visual discrimination task and imaged the activity of PPC populations during both engaged behavior and passive viewing. Unlike neurons in primary visual cortex (V1), which responded robustly to stimuli in both conditions, most neurons in PPC responded exclusively during task engagement. However, PPC responses were heterogeneous, with a smaller subset of neurons exhibiting stimulus-driven, contrast-dependent responses in both conditions. Neurons in PPC also exhibit stronger modulation by noise correlations relative to V1, as illustrated by a generalized linear model that takes into account both task variables and between-neuron correlations. To test whether PPC responses primarily encoded the stimulus or the learned sensorimotor contingency, we imaged the same neurons before and after re-training mice on a reversed task contingency. Unlike V1 neurons, most PPC neurons exhibited a dramatic shift in selectivity after re-training and reflected the new sensorimotor contingency, while a smaller subset of neurons preserved their stimulus selectivity. Mouse PPC is therefore strongly task-dependent, contains heterogeneous populations sensitive to stimulus and choice, and may play an important role in the flexible transformation of sensory inputs into motor commands.\n\nSignificance StatementPerceptual decision making involves both processing of sensory information and mapping that information onto appropriate motor commands via learned sensorimotor associations. While visual cortex (V1) is known to be critical for sensory processing, it is unclear what circuits are involved in the process of sensorimotor transformation. While the mouse posterior parietal cortex (PPC) has been implicated in visual decisions, its specific role has been controversial. By imaging population activity while manipulating task engagement and sensorimotor contingencies, we demonstrate that PPC, unlike V1, is highly task-dependent, heterogeneous, and sensitive to the learned task demands. Our results suggest that PPC is more than a visual area, and may instead be involved in the flexible mapping of visual information onto appropriate motor actions.

neuroscience↗