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Dimwamwa, E.

Publications and source records attributed to Dimwamwa, E..

3 recordsLinked to original sources

Distinct frontal cortical pathways for the long-range processing of auditory and visual stimuli

Frontal cortex neurons are sensory responsive and send long-range feedback to multiple different sensory cortices, but whether these functions are carried out by the same neurons or by distinct modality-specific circuits remains unknown. Using large-scale electrophysiology, two-photon calcium imaging, and viral circuit tracing in awake mice, we identify rich, modality-specific sensory coding in the frontal cortex (secondary motor/anterior cingulate cortex) that is largely dissociated from the neurons providing feedback to sensory cortex. Frontal cortex neurons exhibited robust sensory-evoked activity, with response magnitudes, latencies, and feature selectivity comparable to those observed in primary sensory cortex. Individual neurons displayed tuning for distinct sensory modalities, while population-level activity reliably decoded both sensory modality and stimulus identity. Anatomically, primary auditory (A1) and visual (V1) cortex axons were largely intermingled in anterior frontal cortex but more segregated in posterior regions, revealing spatial variation in the integration of sensory inputs. Frontal cortex neurons responsive to auditory stimuli were biased more anterior compared to visually-responsive neurons. Dual retrograde tracing identified distinct frontal cortex populations projecting back to A1 and V1 that were biased to the posterior and medial extent of the frontal cortex. A1- and V1-projecting frontal neurons were minimally sensory responsive, and no more likely to be responsive than other frontal neurons. Together, these findings reveal a division of labor within the frontal cortex, in which detailed sensory representations and corticocortical feedback arise from partially distinct neuronal populations. This circuit architecture provides a means through which specific sensory information can be transformed within the frontal cortex before being communicated back to the sensory cortex according to behavioral demands.

neuroscience↗

Layer 6 corticothalamic neurons induce high gamma oscillations through cortico-cortical and cortico-thalamo-cortical pathways

Layer 6 corticothalamic (L6CT) neurons project to both cortex and thalamus, inducing multiple effects including the modulation of cortical and thalamic firing, and the emergence of high gamma oscillations in the cortical local field potential (LFP). We hypothesize that the high gamma oscillations driven by L6CT neuron activation are shaped by the dynamic engagement of intracortical and cortico-thalamo-cortical circuits. To test this, we optogenetically activated L6CT neurons in NTSR1-cre mice expressing channelrhodopsin-2 in L6CT neurons. Leveraging the vibrissal pathway in awake, head-fixed mice, we presented ramp-and-hold light at different intensities while recording neural activity in the primary somatosensory barrel cortex (S1) and the ventral posteromedial nucleus (VPm) of the thalamus using silicon probes. We found that the activation of S1 L6CT neurons induces high-frequency LFP oscillations in S1 that are modulated in frequency, but not in amplitude, across light intensities and over time. To identify which neuronal classes contribute to these oscillations, we examined the temporal evolution of firing rate in S1 and VPm. While most S1 neurons were steadily suppressed, VPm and S1 Layer 4 fast spiking (L4 FS) neurons evolved from being suppressed to facilitated within 500 ms, suggesting differential recruitment of the intracortical vs cortico-thalamo-cortical pathways. Finally, we found that LFP frequency selectively correlates with VPm firing rate. Taken together, our data suggest that L6CT neurons sculpt the frequency of S1 LFP high gamma oscillations through cortico-thalamo-cortical circuits, linking the recurrent interactions mediated by L6CT neurons to the high gamma oscillations observed across physiological and pathological conditions. Significance StatementLayer 6 corticothalamic (L6CT) neurons are strategically positioned to modulate the cortex and the thalamus allowing them to engage distinct, yet interlocked, circuits. Here we show that the activation of L6CT neurons in the mouse primary somatosensory cortex induces fast cortical oscillations through the coordinated engagement of cortico-thalamo-cortical and intracortical pathways. Our work reveals that these two L6CT-mediated pathways exert competing effects: while intracortical connections suppress cortical spiking, the activity of the cortico-thalamo-cortical loop rapidly evolves, facilitating cortical spiking. We demonstrate that the cortico-thalamo-cortical pathway operates on a faster timescale than the intracortical pathway and critically shapes cortical oscillation frequency. These findings reveal how the unique position of corticothalamic neurons allows them to flexibly and dynamically modulate the thalamocortical network.

neuroscience↗

Dynamic corticothalamic modulation of the somatosensory thalamocortical circuit during wakefulness

The feedback projections from cortical layer 6 (L6CT) to sensory thalamus have long been implicated in playing a primary role in gating sensory signaling but remain poorly understood. To causally elucidate the full range of effects of these projections, we targeted silicon probe recordings to the whisker thalamocortical circuit of awake mice selectively expressing Channelrhodopsin-2 in L6CT neurons. Through optogenetic manipulation of L6CT neurons, multi-site electrophysiological recordings, and modeling of L6CT circuitry, we establish L6CT neurons as dynamic modulators of ongoing spiking in the ventro-posterior-medial nucleus of thalamus (VPm), either suppressing or enhancing VPm spiking depending on L6CT neurons firing rate and synchrony. Differential effects across the cortical excitatory and inhibitory sub-populations point to an overall influence of L6CT feedback on cortical excitability that could have profound implications for regulating sensory signaling across a range of ethologically relevant conditions.

neuroscience↗