Biology subjects

Gritton, H. J.

Publications and source records attributed to Gritton, H. J..

8 recordsLinked to original sources

bioRxiv2023

`Mind in Vitro' platforms: Versatile, scalable, robust and open solutions to interfacing with living neurons

Motivated by the unexplored potential of in vitro neural systems for computing, and by the corresponding need of versatile, scalable interfaces for multimodal interaction, we present an accurate, modular, fully customizable and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated. A reconfigurable platform that works across multiple industry standards enables a complete signal chain, from neural substrates sampled through high-density Micro-Electrode Arrays (MEAs) to data acquisition, downstream analysis and cloud storage. Built-in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations and spatial topologies. Through a native analysis and management software suite, the utility and robustness of our system is demonstrated across neural cultures and applications, including embryonic stem cell-derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging and long-term recording. Overall, our technology, termed Mind in Vitro to underscore the computing inspiration, provides an end-to-end solution that can be widely deployed due to its affordable (>10X cost-reduction) and open-source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.

neuroscience↗

bioRxiv2022

A Robust, Compact and Diverse Population Code for Competing Sounds in Auditory Cortex

Cortical circuits encoding sensory information consist of populations of neurons, yet how information aggregates via pooling individual cells remains poorly understood. Such pooling may be particularly important in noisy settings where single neuron encoding is degraded. One example is the cocktail party problem, with competing sounds from multiple spatial locations. How populations of neurons in auditory cortex (ACx) code competing sounds have not been previously investigated. Here, we apply a novel information theoretic approach to estimate information in populations of neurons in ACx about competing sounds from multiple spatial locations, including both summed population (SP) and labeled line (LL) codes. We find that a small subset of neurons is sufficient to nearly maximize mutual information over different spatial configurations, with the LL code outperforming the SP code, and approaching information levels attained without noise. Moreover, with a LL code, units with diverse spatial responses, including both regular and narrow-spiking units, constitute the best pool. Finally, information in the population increases with spatial separation between target and masker, in correspondence with behavioral results on spatial release from masking in human and animals. Taken together, our results reveal that a compact and diverse population of neurons in ACx provide a robust code for competing sounds from different spatial locations.

neuroscience↗

bioRxiv2021

PV neurons improve cortical complex scene analysis by enhancing timing-based coding

Cortical representations supporting many cognitive abilities emerge from underlying circuits comprised of several different cell types. However, cell type-specific contributions to rate and timing-based cortical coding are not well-understood. Here, we investigated the role of parvalbumin (PV) neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli which are highly dynamic in time and compete with stimuli at other spatial locations. PV neurons play a fundamental role in balancing excitation and inhibition in cortex and sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based coding, and the robustness of temporal representations to spatial competition, has not been investigated. Here, we address these questions in auditory cortex using a cocktail party-like paradigm, integrating electrophysiology, optogenetic manipulations, and a family of spike-distance metrics, to dissect PV neurons contributions towards rate and timing-based coding. We find that suppressing PV neurons degrades cortical discrimination of dynamic sounds in a cocktail party-like setting via changes in rapid temporal modulations in rate and spike timing, over a wide range of time-scales. Our findings suggest that PV neurons play a critical role in enhancing cortical temporal coding and reducing cortical noise, thereby improving representations of dynamic stimuli in complex scenes. Significance StatementOne impressive example of sensory perception by the brain is its ability to analyze complex scenes, e.g., following what a friend is saying at a party amongst other speakers. Although some humans can solve this problem with relative ease, it remains very difficult for humans with a variety of impairments, e.g., hearing impairments, ADHD, and autism. The brain mechanisms underlying complex scene analysis remain poorly understood. Here, we recorded neural activity in auditory cortex in a complex auditory scene. When we suppressed PV neuron activity in auditory cortex, cortical performance decreased, and the timing of cortical responses was degraded. Our findings suggest that PV neurons improve the brains ability to analyze complex scenes by enhancing the timing of cortical responses while reducing cortical noise.

neuroscience↗

bioRxiv2021

Large-scale cellular-resolution imaging of neural activity in freely behaving mice

Miniaturized microscopes for head-mounted fluorescence imaging are powerful tools for visualizing neural activity during naturalistic behaviors, but the restricted field of view of first-generation miniscopes limits the size of neural populations accessible for imaging. Here we describe a novel miniaturized mesoscope offering cellular-resolution imaging over areas spanning several millimeters in freely moving mice. This system enables comprehensive visualization of activity across entire brain regions or interactions across areas.

neuroscience↗

bioRxiv2020

Oscillatory activity in alpha/beta frequencies coordinates auditory and prefrontal cortices during extinction learning

Cortical synchrony is theorized to contribute to communication between connected networks during executive functioning. To understand the functional role of neural synchrony in cognitive flexibility, we recorded from auditory cortex (AC) and medial prefrontal cortex (mPFC), while mice performed an auditory extinction learning task. We found that while animals gradually showed reduced responding to the unrewarded tone over hundreds of trials, the power of local field potential (LFP) oscillations (8-18 Hz, centered at alpha/beta frequencies) in AC and mPFC exhibited immediate and robust increases, prior to behavioral changes. The strength of LFP alpha/beta power in the mPFC, but not AC, was strongly correlated with the behavioral performance that mice would achieve later in the training session. Further, we found that coherence between AC and mPFC at 8-18Hz was selectively enhanced only after mice learned to suppress licking, and this LFP coherence increase coincided with a reduction in spiking rate for the unrewarded tone in AC. These results reveal that enhanced interactions between PFC and AC is an inherent property of auditory discrimination learning, and that coordinated alpha/beta oscillations contribute to cognitive flexibility.

neuroscience↗

bioRxiv2020

Distinct Neuronal Populations Contribute to Trace Conditioning and Extinction Learning in the Hippocampal CA1

Trace conditioning and extinction learning depend on the hippocampus, but it remains unclear how ongoing neural activities in the hippocampus are modulated during different learning processes. To explore this question, we performed calcium imaging in a large number of individual CA1 neurons during both trace eye-blink conditioning and subsequent extinction learning in mice. Using trial-averaged calcium fluorescence analysis, we found direct evidence that in real time, as learning emerges, distinct populations of CA1 cells contribute to trace conditioned learning versus extinction learning. Furthermore, we examined network connectivity by calculating co-activity between CA1 neuron pairs, and found that CA1 network connectivity is different between conditioning and extinction and between correct versus incorrect behavioral responses during trace conditioned learning. However, the overall connectivity density remains constant across these behavioral conditions. Together, our results demonstrate that distinct populations of CA1 neurons, forming different sub-networks with unique connectivity patterns, encode different aspects of learning.

neuroscience↗

bioRxiv2019

Population imaging of neural activity in awake behaving mice in multiple brain regions

A longstanding goal in neuroscience has been to image membrane voltage, with high temporal precision and sensitivity, in awake behaving mammals. Here, we report a genetically encoded voltage indicator, SomArchon, which exhibits millisecond response times and compatibility with optogenetic control, and which increases the sensitivity, signal-to-noise ratio, and number of neurons observable, by manyfold over previous reagents. SomArchon only requires conventional one-photon microscopy to achieve these high performance characteristics. These improvements enable population analysis of neural activity, both at the subthreshold and spiking levels, in multiple brain regions - cortex, hippocampus, and striatum - of awake behaving mice. Using SomArchon, we detect both positive and negative responses of striatal neurons during movement, highlighting the power of voltage imaging to reveal bidirectional modulation. We also examine how the intracellular subthreshold theta oscillations of hippocampal neurons govern spike output, finding that nearby cells can exhibit highly correlated subthreshold activities, even as they generate highly divergent spiking patterns.

neuroscience↗

bioRxiv2018

Muscarinic receptors regulate auditory and prefrontal cortical communication during auditory processing

Much of our understanding about how acetylcholine modulates prefrontal cortical (PFC) networks comes from behavioral experiments that examine cortical dynamics during highly attentive states. However, much less is known about how PFC is recruited during passive sensory processing and how acetylcholine may regulate connectivity between cortical areas outside of task performance. To investigate the involvement of PFC and cholinergic neuromodulation in passive auditory processing, we performed simultaneous recordings in the auditory cortex (AC) and PFC in awake head fixed mice presented with a white noise auditory stimulus in the presence or absence of local cholinergic antagonists in AC. We found that a subset of PFC neurons were strongly driven by auditory stimuli even when the stimulus had no associative meaning, suggesting PFC monitors stimuli under passive conditions. We also found that cholinergic signaling in AC shapes the strength of auditory driven response in PFC, by modulating the intra-cortical sensory response through muscarinic interactions in AC. Taken together, these findings provide novel evidence that cholinergic mechanisms have a continuous role in cortical gating through muscarinic receptors during passive processing and expand traditional views of prefrontal cortical function and the contributions of cholinergic modulation in sensory gating.\n\nHighlightsO_LIPrefrontal cortex actively monitors non-associative stimuli under passive conditions\nC_LIO_LIAcetylcholine facilitates cortical signaling even outside of attentional contexts\nC_LIO_LILocal scopolamine infusion reduced intracortical signaling and impaired cortical gating\nC_LIO_LImAChR have an ongoing role in sound processing\nC_LI

neuroscience↗