Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.07.17.665299

Corticothalamic Layer 6 Controls Cortical Activity and Thalamic Firing Mode in a Bidirectional Manner

Abstract

Corticothalamic layer 6 modulates information flow between cortical and thalamic circuits. Previous research reported contrasting inhibitory or excitatory effects of corticothalamic layer 6 on cortical dynamics, potentially reflecting technological discrepancies or physiological differences in corticothalamic layer 6 function. To resolve these discrepancies, we combined translaminar, multi-channel in vivo electrophysiology in the primary somatosensory cortex of the anaesthetised mouse with optogenetic stimulation across a range of stimulation regimes to manipulate firing rate and frequency of corticothalamic layer 6. Increasing corticothalamic layer 6 firing rates exerted a transition from inhibition to excitation across cortical layers. Furthermore, corticothalamic layer 6 activity imparted population synchrony onto distinct cortical subpopulations, independent of changes in overall corticothalamic layer 6 activity. In the thalamus, corticothalamic layer 6 modulated thalamic bursting in a bidirectional manner, dependent on optogenetic stimulation frequency. These results demonstrate that corticothalamic layer 6 in primary somatosensory cortex can bidirectionally modulate both cortical firing and thalamic firing mode, elucidating a more nuanced function of somatosensory corticothalamic layer 6 in thalamic and cortical signalling than previously recognised.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Folkard, R., Isaias-Camacho, E. U., Groh, A.. 2025-07-21. Corticothalamic Layer 6 Controls Cortical Activity and Thalamic Firing Mode in a Bidirectional Manner. https://doi.org/10.1101/2025.07.17.665299

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Sleep spindles stabilize human thalamocortical networks, inhibiting pathological disruptions

The thalamus coordinates sleep-dependent brain function including memory consolidation, sensory gating, and network stability through spindle oscillations. Thalamocortical circuits are also affected in many neurological and neuropsychiatric disorders. Yet how human thalamocortical circuits respond to pathological disruptions remain poorly understood. Here, we leveraged interictal epileptiform discharges (IEDs) as spontaneous perturbations to probe spindle-generating circuits and thalamocortical dynamics in vivo. Using multi-night intracranial recordings spanning multiple thalamic nuclei and cortical regions in 55 individuals with epilepsy, we investigated interactions between sleep spindles and epileptic activity across timescales from milliseconds to days. Sleep spindles were associated with IED suppression, whereas IEDs increased subsequent spindle probability, revealing bidirectional interactions between physiological and pathological activity. Nights with lower IEDs corresponded to increased spindle occurrence, longer duration, and faster frequency, reflecting a more stable thalamocortical state. These findings propose sleep spindles as potential regulators of thalamocortical networks that actively respond to and regulate pathological activity.

neuroscience↗

Hippocampal interferon-response, unfolded-protein-response and synaptic transcriptional signatures in RORγt-transgenic mice

Aim: ROR{gamma}t-transgenic mice provide a model of sustained T helper 17-cell bias, but the associated hippocampal transcriptional profile is incompletely characterized. We investigated gene-level and gene-set expression differences in this model. Methods: Bilateral hippocampal samples from 10-week-old male ROR{gamma}t-transgenic mice and wild-type littermates (n = 3 per genotype) underwent bulk RNA sequencing. Gene-level differential expression was evaluated using the Empirical Analysis of DGE tool in CLC Genomics Workbench. Preranked gene set enrichment analysis examined coordinated expression differences after expression filtering and exclusion of Rorc (13,813 genes). Results: Sixteen genes met a false discovery rate < 0.05 (nine higher and seven lower in transgenic mice), including Rorc, C4b, Xbp1, Nptx2 and Mt2. Of 212 candidates selected using unadjusted P < 0.05 and a twofold-change threshold, 155 (73.1%) had a mean expression below 0.5 reads per kilobase of transcript per million mapped reads. Hallmark interferon--response, interferon-{gamma}-response, and unfolded-protein-response gene sets showed positive enrichment. Thirteen Gene Ontology biological-process sets met a false discovery rate < 0.05, including negatively enriched sets related to excitatory postsynaptic potential, glutamatergic transmission, and calcineurin-mediated signaling. Il17a and Il17f had zero reported counts, and none of the displayed leukocyte or central nervous system cell-marker genes met false discovery rate < 0.05. Conclusion: This exploratory dataset identifies interferon-response, unfolded-protein-response and synaptic transcriptional signatures associated with the ROR{gamma}t-transgenic genotype. The cellular sources, causal mediators and functional consequences remain unresolved.

neuroscience↗

Superficial spinal Tac1-lineage neurons are polymodal nociceptive

Tac1-lineage neurons in the spinal dorsal horn have been implicated in coping behavior in response to sustained noxious stimuli, but their developmental origin, cellular heterogeneity, and functional contribution remain incompletely understood. Here, we characterized the molecular identity, developmental trajectory, electrophysiological properties, and sensory responses of spinal Tac1-lineage neurons. In adults, Tac1-lineage neurons comprised a heterogeneous population of excitatory and inhibitory interneurons and excitatory projection neurons distributed across the superficial dorsal horn. In contrast, at embryonic day 16.5, Tac1-lineage neurons in laminae I/IIo were exclusively projection neurons, revealing a marked developmental transition in the composition of the Tac1 lineage. Electrophysiological recordings from spinal cord slices further demonstrated substantial functional heterogeneity, with most Tac1-lineage neurons exhibiting phasic or single-spike firing and smaller populations displaying tonic or reluctant firing. In vivo calcium imaging in anesthetized mice revealed prominent responses to noxious mechanical and thermal stimulation. Interestingly, Tac1-lineage neurons used distinct strategies to encode cold and heat intensity. Together, these findings reveal pronounced developmental and functional heterogeneity within the Tac1 lineage and demonstrate that adult Tac1-lineage neurons are predominately polymodal nociceptive.

neuroscience↗