Biology subjects

Cammarata, C. M.

Publications and source records attributed to Cammarata, C. M..

3 recordsLinked to original sources

bioRxiv2025

Synaptic dynamics govern spatial integration in mouse visual cortex

Neurons in primary visual cortex are often suppressed by stimuli extending beyond their receptive fields. This surround suppression is proposed to reduce the redundancy of encoding large stimuli and support scene segmentation. We find that surround suppression decreases firing rates in mouse primary visual cortex by accelerating the decay of visually-evoked responses and reducing response duration. The rapid decay of visual responses at large sizes is enhanced by increased contrast, reduced by locomotion, and invariant to stimulus orientation, consistent with the engagement of a network mechanism. While fast-spiking interneurons have faster dynamics relative to neighboring pyramidal cells, the dynamics of somatostatin-expressing interneurons are delayed. At the subthreshold level, the rapid decay of visual responses with increasing size is due to a delayed removal of both synaptic excitation and inhibition below baseline levels following visual input. We propose that the delayed activation of somatostatin-expressing interneurons drives a network-wide suppression and accelerates the decay of the visual response. Thus, these data identify a key role for synaptic network dynamics in regulating both spatial and temporal integration in mouse visual cortex.

neuroscience↗

bioRxiv2024

Behavioral state and stimulus strength regulate the role of somatostatin interneurons in stabilizing network activity

Inhibition stabilization enables cortical circuits to encode sensory signals across diverse contexts. Somatostatin-expressing (SST) interneurons are well-suited for this role through their strong recurrent connectivity with excitatory pyramidal cells. We developed a cortical circuit model predicting that SST cells become increasingly important for stabilization as sensory input strengthens. We tested this prediction in mouse primary visual cortex by manipulating excitatory input to SST cells, a key parameter for inhibition stabilization, with a novel cell-type specific pharmacological method to selectively block glutamatergic receptors on SST cells. Consistent with our model predictions, we find antagonizing glutamatergic receptors drives a paradoxical facilitation of SST cells with increasing stimulus contrast. In addition, we find even stronger engagement of SST-dependent stabilization when the mice are aroused. Thus, we reveal that the role of SST cells in cortical processing gradually switches as a function of both input strength and behavioral state.

neuroscience↗

bioRxiv2022

Thousandfold Cell-Specific Pharmacology of Neurotransmission

Cell-specific pharmaceutical technologies promise mechanistic insight into clinical drugs[-]those that treat, and often define, human disease. In particular, DART (drug acutely restricted by tethering) achieves genetically programmable control of drug concentration over cellular dimensions. The method is compatible with clinical pharmaceuticals and amenable to studies in behaving animals. Here, we describe DART.2, comprising three advances. First, we improve the efficiency of chemical capture, enabling cell-specific accumulation of drug to [~]3,000-times the ambient concentration in 15 min. Second, we develop tracer reagents, providing a behavior-independent measure of cellular target engagement in each animal. Third, we extend the method to positive allosteric modulators and outline design principles for this clinically significant class. We showcase the platform with four pharmaceuticals[-]two that weaken excitatory (AMPAR) or inhibitory (GABAAR) chemical neurotransmission, and two that strengthen these forms of synaptic communication. Across four labs, we tested reagents in the mouse cerebellum, basal ganglia, visual cortex, and retina. Collectively, we demonstrate robust, bidirectional editing of chemical neurotransmission. We provide for distribution of validated reagents, community design principles, and synthetic building blocks for application to diverse pharmaceuticals.

neuroscience↗