Biology subjects

Hull, J. M.

Publications and source records attributed to Hull, J. M..

5 recordsLinked to original sources

bioRxiv2025

Beyond seizure control: identifying deficits in cognitive networks in absence seizure.

Absence epilepsy is frequently associated with cognitive impairments, yet the direct or indirect involvement of cognitive circuits remains poorly understood, as spike-and-wave discharges are rarely reported in these regions. Here, we investigate the role of a thalamic-prefrontal pathway in a mouse model of absence epilepsy (Scn8a+/-). We find that Scn8a+/- mice exhibit deficits in reversal learning, along with impaired recruitment of medial prefrontal cortex (mPFC) neurons by the Reuniens nucleus of the thalamus. This deficit is accompanied by an altered excitation-inhibition balance and reduced excitability of layer I interneurons in the mPFC, which constitutes the main recipient zone of reuniens inputs to the mPFC. Remarkably, stimulation of Reuniens at 20 Hz significantly reduces seizure incidence and improves performance in reversal learning. Our findings reveal previously unrecognized cognitive circuit dysfunctions in absence epilepsy and highlight the thalamo-prefrontal axis as a promising target for both cognitive and seizure-related interventions.

neuroscience↗

bioRxiv2025

Interpretable Machine Learning Identifies an Emergent Absence Seizure Mechanism

Absence seizures are widespread spike-and-wave oscillations disrupting consciousness. Several consciousness frameworks emphasize intercortical/thalamocortical feedback dynamics, but we lack explicit dynamical mechanisms for how seizures disrupt these circuits. Using interpretable machine learning, we derived dynamical equations directly from seizure electrocorticogram data, reproducing seconds-long multi-regional local field potentials with precision matching inter-mouse variability. The model contained a low-dimensional chaotic seizure attractor emerging from between-region synchronization at preferred phase-lags. Unit recordings revealed corresponding spiking synchrony at single-neuron resolution, linking somatosensory and motor cortex with posterior thalamic nucleus (PO). Model coupling terms predicted tonic and burst firing spatiotemporal organization across regions and guided multisite-optogenetic stimulations. These stimulations showed PO controls corticocortical connectivity gain and that motor/somatosensory corticocortical functional connectivity varies at predicted phase-lags to drive seizures. Our results define absence seizures as dynamics confined to a chaotic attractor within a circuit implicated in anesthetic unconsciousness, linking distributed network chaos to loss of consciousness.

neuroscience↗

bioRxiv2024

Reuniens thalamus recruits recurrent excitation in medial prefrontal cortex.

Medial prefrontal cortex (mPFC) and hippocampus are critical for memory retrieval, decision making and emotional regulation. While ventral CA1 (vCA1) shows direct and reciprocal connections with mPFC, dorsal CA1 (dCA1) forms indirect pathways to mPFC, notably via the thalamic Reuniens nucleus (Re). Neuroanatomical tracing has documented structural connectivity of this indirect pathway through Re however, its functional operation is largely unexplored. Here we used in vivo and in vitro electrophysiology along with optogenetics to address this question. Whole-cell patch-clamp recordings in acute mouse brain slices revealed both monosynaptic excitatory responses and disynaptic feedforward inhibition at Re-mPFC synapses. However, we also identified a novel prolonged excitation of mPFC by Re. These early monosynaptic and late recurrent components are in marked contrast to the primarily feedforward inhibition characteristic of thalamic inputs to neocortex. Local field potential recordings in mPFC brain slices revealed prolonged synaptic activity throughout all cortical lamina upon Re activation, with the late excitation enhanced by blockade of parvalbumin neurons and GABAARs. In vivo Neuropixels recordings in head-fixed awake mice revealed a similar prolonged excitation of mPFC units by Re activation. In summary, Re output produces recurrent feedforward excitation within mPFC suggesting a potent amplification system in the Re-mPFC network. This may facilitate amplification of dCA1->mPFC signals for which Re acts as the primary conduit, as there is little direct connectivity. In addition, the capacity of mPFC neurons to fire bursts of action potentials in response to Re input suggests that these synapses have a high gain. Significance statementThe interactions between medial prefrontal cortex and hippocampus are crucial for memory formation and retrieval. Yet, it is still poorly understood how the functional connectivity of direct and indirect pathways underlies these functions. This research explores the synaptic connectivity of the indirect pathway through the Reuniens nucleus of the thalamus using electrophysiological recordings and optogenetic manipulations. The study found that Reuniens stimulation recruits recurrent and long-lasting activity in mPFC - a phenomenon not previously recorded. This recurrent activity might create a temporal window ideal for coincidence detection and be an underlying mechanism for memory formation and retrieval.

neuroscience↗

bioRxiv2020

Environmental DNA sampling provides new management strategies for vernal pool branchiopods in California

Californias vernal pools are declining ecosystems that support valuable native plant and animal diversity. Vernal pool branchiopods are particularly at risk from vernal pool habitat loss and conservation efforts have targeted their long-term protection through the establishment of preserves and conservation banks. These conservation strategies require repeated, perpetual monitoring of preserved habitat, which is currently carried out through dip-net surveys and visual identification of specimens. Dip-netting may be destructive and frequently requires some sacrifice of protected species. Environmental DNA offers a new, modern method to monitor many protected freshwater organisms. We designed qPCR-based species-specific assays for four of Californias vernal pool branchiopods: The Vernal Pool Fairy Shrimp Branchinecta lynchi (BRLY), the Midvalley Fairy Shrimp Branchinecta mesovallensis (BRME), and the Conservancy Fairy Shrimp Branchinecta conservatio (BRCO), and the Vernal Pool Tadpole Shrimp Lepidurus packardi (LEPA). We tested these assays using eDNA sampling protocols alongside traditional dip-net surveys to assess their viability as an alternative method to monitor vernal pool branchiopods. Based on occupancy modeling, each of our assays achieved a 95% or higher detection rate when using optimized sampling protocols.

genetics↗

bioRxiv2020

Dscam gene triplication causes neocortical overinhibition in Down syndrome

A growing number of molecules have been identified as regulators of inhibitory synapse development, but whether dysregulated expression of these molecules contribute to brain disorders is poorly understood. Here we show that Down syndrome cell adhesion molecule (Dscam) regulates the inhibition of neocortical pyramidal neurons (PyNs) in a level-dependent fashion. Loss of Dscam impairs inhibitory neuron development and function. In the Ts65Dn mouse model for Down syndrome, where Dscam is overexpressed, GABAergic innervation of cortical PyNs by chandelier and basket cells is increased. Genetic normalization of Dscam expression rescues the excessive GABAergic innervation and the increased inhibition of PyNs. These findings demonstrate excessive GABAergic innervation and inhibition in the neocortex of Down syndrome mouse model and identify Dscam overexpression as the cause. They also implicate dysregulated Dscam levels as a potential pathogenic driver in related neurological disorders.

neuroscience↗