Biology subjects

Forest, C. R.

Publications and source records attributed to Forest, C. R..

3 recordsLinked to original sources

bioRxiv2020

Inferring Monosynaptic Connectivity Across Brain Structures In-Vivo

Abstract/SummaryAs the tools to simultaneously record electrophysiological signals from large numbers of neurons within and across brain regions become increasingly available, this opens up for the first time the possibility of establishing the details of causal relationships between monosynaptically connected neurons and the patterns of neural activation that underlie perception and behavior. Although recorded activity across synaptically connected neurons has served as the cornerstone for much of what we know about synaptic transmission and plasticity, this has largely been relegated to ex-vivo preparations that enable precise targeting under relatively well-controlled conditions. Analogous studies in-vivo, where image-guided targeting is often not yet possible, rely on indirect, data-driven measures, and as a result such studies have been sparse and the dependence upon important experimental parameters has not been well studied. Here, using in-vivo extracellular single unit recordings in the topographically aligned rodent thalamocortical pathway, we sought to establish a general experimental and computational framework for inferring synaptic connectivity. Specifically, attacking this problem within a statistical signal-detection framework utilizing experimentally recorded data in the ventral-posterior medial (VPm) region of the thalamus and the homologous region in layer 4 of primary somatosensory cortex (S1) revealed a trade-off between network activity levels needed for the data-driven inference and synchronization of nearby neurons within the population that result in masking of synaptic relationships. Taken together, we provide a framework for establishing connectivity in multi-site, multi-electrode recordings based on statistical inference, setting the stage for large-scale assessment of synaptic connectivity within and across brain structures. New & NoteworthyDespite the fact that all brain function relies on the long-range transfer of information across different regions, the tools enabling us to measure connectivity across brain structures are lacking. Here, we provide a statistical framework for identifying and assessing potential monosynaptic connectivity across neuronal circuits from population spiking activity that generalizes to large-scale recording technologies that will help us to better understand the signaling within networks that underlies perception and behavior.

neuroscience↗

bioRxiv2020

Rapid Cortical Adaptation and the Role of Thalamic Synchrony During Wakefulness

Rapid sensory adaptation is observed across all sensory systems, and strongly shapes sensory percepts in complex sensory environments. Yet despite its ubiquity and likely necessity for survival, the mechanistic basis is poorly understood. A wide range of primarily in-vitro and anesthetized studies have demonstrated the emergence of adaptation at the level of primary sensory cortex, with only modest signatures in earlier stages of processing. The nature of rapid adaptation and how it shapes sensory representations during wakefulness, and thus the potential role in perceptual adaptation, is underexplored, as are the mechanisms that underlie this phenomenon. To address these knowledge gaps, we recorded spiking activity in primary somatosensory cortex (S1) and the upstream ventral posteromedial (VPm) thalamic nucleus in the vibrissa pathway of awake male and female mice, and quantified responses to whisker stimuli delivered in isolation and embedded in an adapting sensory background. We found that cortical sensory responses were indeed adapted by persistent sensory stimulation; putative excitatory neurons were profoundly adapted, and inhibitory neurons only modestly so. Further optogenetic manipulation experiments and network modeling suggest this largely reflects adaptive changes in synchronous thalamic firing combined with robust engagement of feedforward inhibition, with little contribution from synaptic depression. Taken together, these results suggest that cortical adaptation in the regime explored here results from changes in the timing of thalamic input, and the way in which this differentially impacts cortical excitation and feedforward inhibition, pointing to a prominent role of thalamic gating in rapid adaptation of primary sensory cortex. Significance StatementRapid adaptation of sensory activity strongly shapes representations of sensory inputs across all sensory pathways over the timescale of seconds, and has profound effects on sensory perception. Despite its ubiquity and theoretical role in the efficient encoding of complex sensory environments, the mechanistic basis is poorly understood, particularly during wakefulness. In this study in the vibrissa pathway of awake mice, we show that cortical representations of sensory inputs are strongly shaped by rapid adaptation, and that this is mediated primarily by adaptive gating of the thalamic inputs to primary sensory cortex and the differential way in which these inputs engage cortical sub-populations of neurons.

neuroscience↗

bioRxiv2020

Compensation of physiological motion enables high-yield whole-cell recording in vivo

1.1.1Whole-cell patch-clamp recording in vivo is the gold-standard method for measuring subthreshold electrophysiology from single cells during behavioural tasks, sensory stimulations, and optogenetic manipulation. However, these recordings require a tight, gigaohm resistance, seal between a glass pipette electrodes aperture and a cells membrane. These seals are difficult to form, especially in vivo, in part because of a strong dependence on the distance between the pipette aperture and cell membrane. We elucidate and utilize this dependency to develop an autonomous method for placement and synchronization of pipettes tip aperture to the membrane of a nearby, moving neuron, which enables high-yield seal formation and subsequent recordings in the deep in the brain of the living mouse, in the thalamus. This synchronization procedure nearly doubles the reported gigaseal yield in the thalamus (>3 mm below the pial surface) from 26% (n=17/64) to 48% (n=32/66). Whole-cell recording yield improved from 10% (n = 9/88) to 24% (n=18/76) when motion compensation was used during the gigaseal formation. As an example of its application, we utilized this system to investigate the role of the sensory environment and ventral posterior medial region (VPM) projection synchrony on intracellular dynamics in the barrel cortex. This method results in substantially greater subcortical whole-cell recording yield than previously reported and thus makes pan-brain whole-cell electrophysiology practical in the living mouse brain.

neuroscience↗