Interneurons exhibit attenuated ectopic action potential firing in a severe neurodevelopmental disorder.

Dravet syndrome (DS) is a severe neurodevelopmental disorder associated with treatment-resistant epilepsy and features of autism spectrum disorder due to loss of the voltage-gated sodium channel subunit Nav1.1. Recent work suggests that a pathogenic mechanism of DS is impaired action potential propagation along axons of cerebral cortex parvalbumin-positive fast-spiking GABAergic interneurons (PVINs).

Activity-Dependent Ectopic Spiking in Parvalbumin-Expressing Interneurons of the Neocortex.

Canonically, action potentials of most mammalian neurons initiate at the axon initial segment (AIS) and propagate bidirectionally: orthodromically along the distal axon and retrogradely into the soma and dendrites. Under some circumstances, action potentials may initiate ectopically, at sites distal to the AIS, and propagate antidromically along the axon. These "ectopic action potentials" (EAPs) have been observed in experimental models of seizures and chronic pain, and more rarely in nonpathological forebrain neurons.

Activity-dependent ectopic action potentials in regular-spiking neurons of the neocortex.

Introduction: Action potentials usually travel orthodromically along a neuron's axon, from the axon initial segment (AIS) toward the presynaptic terminals. Under some circumstances action potentials also travel in the opposite direction, antidromically, after being initiated at a distal location. Given their initiation at an atypical site, we refer to these events as "ectopic action potentials.

Thalamic neuromodulation in epilepsy: A primer for emerging circuit-based therapies.

Introduction: Epilepsy is a common, often debilitating disease of hyperexcitable neural networks. While medically intractable cases may benefit from surgery, there may be no single, well-localized focus for resection or ablation. In such cases, approaching the disease from a network-based perspective may be beneficial.

Early Life Stress Drives Sex-Selective Impairment in Reversal Learning by Affecting Parvalbumin Interneurons in Orbitofrontal Cortex of Mice.

Poverty, displacement, and parental stress represent potent sources of early life stress (ELS). Stress disproportionately affects females, who are at increased risk for stress-related pathologies associated with cognitive impairment. Mechanisms underlying stress-associated cognitive impairment and enhanced risk of females remain unknown.

In vitro imaging using laser photostimulation with flavoprotein autofluorescence.

Imaging of 300-500 μm mouse brain slices by laser photostimulation with flavoprotein autofluorescence (LFPA) allows the rapid and sensitive mapping of neuronal connectivity. It is accomplished using UV laser-based photo-uncaging of glutamate and imaging neuronal activation by capturing changes in green light (∼520 nm) emitted under blue light (∼460 nm) excitation. This fluorescence is generated by the oxidized form of flavoprotein and is a measure of metabolic activity.

Network variability across human tissue samples in vitro: the problem and a solution.

Slices prepared from cortical tissue that is surgically removed from patients to treat their epilepsy provide an opportunity to directly study the mechanisms underlying ictal activity. However, human in vitro studies have several limitations. One problem that may severely compromise investigations of network properties in these slices relates to how difficult it is to cut the tissue at angles that optimally preserve columnar connectivity.

Specific and nonspecific thalamocortical connectivity in the auditory and somatosensory thalamocortical slices.

Two classes of thalamic nuclei project to either middle layers or upper layers, including layer 1, of the neocortex, and are referred to as 'specific' and 'nonspecific' nuclei, respectively. The electrophysiological properties of the nonspecific nuclei have not been investigated, largely because of the paucity of in vitro slice preparations containing intact nonspecific pathways. In this study, we used flavoprotein autofluorescence imaging to show intact thalamocortical connectivity of nonspecific nuclei in slice preparations of the somatosensory and auditory systems.

The corticothalamocortical circuit drives higher-order cortex in the mouse.

An unresolved question in neuroscience relates to the extent to which corticothalamocortical circuits emanating from layer 5B are involved in information transfer through the cortical hierarchy. Using a new form of optical imaging in a brain slice preparation, we found that the corticothalamocortical pathway drove robust activity in higher-order somatosensory cortex. When the direct corticocortical pathway was interrupted, secondary somatosensory cortex showed robust activity in response to stimulation of the barrel field in primary somatosensory cortex (S1BF), which was eliminated after subsequently cutting the somatosensory thalamus, suggesting a highly efficacious corticothalamocortical circuit.