Preferential superficial cortical layer activation during seizure propagation.

Objective: Focal cortical seizures travel long distances from the onset zone, but the long-distance propagation pathways are uncertain. In vitro and in vivo imaging techniques have investigated the local spread of seizures but did not elucidate long-distance spread. Furthermore, classical studies in slices suggested seizure spread locally along deep cortical layers, whereas more recent in vivo imaging studies posit a role for superficial cortical layers in local spread.

Neuronal plasticity contributes to postictal death.

Repeated generalized tonic-clonic seizures (GTCSs) are the most critical risk factor for sudden unexpected death in epilepsy (SUDEP). GTCSs can cause fatal apnea. We investigated neuronal plasticity mechanisms that precipitate postictal apnea and seizure-induced death.

Connectivity and Excitability Shape Seizure Circuits.

Mapping neuronal circuits that generate focal to bilateral tonic-clonic seizures is essential for understanding general principles of seizure propagation and modifying the risk of death and injury due to bilateral motor seizures. We used novel techniques developed over the past decade to study these circuits. We propose the general hypothesis that at the mesoscale, seizures follow anatomical projections of the seizure focus, preferentially activating more excitable neurons.

Extrahippocampal seizure and memory circuits overlap.

Seizures cause retrograde amnesia. We have previously demonstrated that seizures erode recently formed memories through shared ensembles and mechanisms in the CA1 region of the hippocampus. Here, we tested whether seizure circuits overlap spatial memory circuits outside of the CA.

Construction of Local Field Potential Microelectrodes for in vivo Recordings from Multiple Brain Structures Simultaneously.

Researchers often need to record local field potentials (LFPs) simultaneously from several brain structures. Recording from multiple desired brain regions requires different microelectrode designs, but commercially available microelectrode arrays often do not offer such flexibility. Here, the present protocol outlines the straightforward design of custom-made microelectrode arrays to record LFPs from multiple brain structures simultaneously at different depths.

Distinct Roles of Rodent Thalamus and Corpus Callosum in Seizure Generalization.

Objective: Bilateral synchronous cortical activity occurs during sleep, attention, and seizures. Canonical models place the thalamus at the center of bilateral cortical synchronization because it generates bilateral sleep spindle oscillations and primarily generalized absence seizures. However, classical studies suggest that the corpus callosum mediates bilateral cortical synchronization.

Anticonvulsant dopamine type 2 receptor agonist activates inhibitory parvalbumin interneurons.

Dopamine type 2 receptor (D2R) agonists have anticonvulsant effect, whereas D2R antagonists increase seizure risk, but the mechanism of this action has not been delineated. We tested whether D2R agonists activate parvalbumin (PV)-containing inhibitory interneurons to suppress seizures. We treated frontal lobe onset seizures with a D2R agonist sumanirole, and it suppressed seizures.

Connectivity and Neuronal Synchrony during Seizures.

There is uncertainty regarding when and which groups of neurons fire synchronously during seizures. While several studies found heterogeneous firing during seizures, others suggested synchronous neuronal firing in the seizure core. We tested whether neuronal activity during seizures is orderly in the direction of the excitatory neuronal connections in the circuit.

Activation of the basal ganglia and indirect pathway neurons during frontal lobe seizures.

There are no detailed descriptions of neuronal circuit active during frontal lobe motor seizures. Using activity reporter mice, local field potential recordings, tissue clearing, viral tracing, and super-resolution microscopy, we found neuronal activation after focal motor to bilateral tonic-clonic seizures in the striatum, globus pallidus externus, subthalamic nucleus, substantia nigra pars reticulata and neurons of the indirect pathway. Seizures preferentially activated dopamine D2 receptor-expressing neurons over D1 in the striatum, which have different projections.

Circuits generating secondarily generalized seizures.

Mapping the circuits underlying the generation and propagation of seizures is critically important for understanding their pathophysiology. We review evidence to suggest that circuits engaged in secondarily generalized seizures are likely to be more complex than those currently proposed. Focal seizures have been proposed to engage canonical thalamocortical circuits that mediate primarily generalized absence seizures, leading to secondarily generalized tonic-clonic seizures.

Parallel pathways of seizure generalization.

Generalized convulsive status epilepticus is a life-threatening emergency, because recurrent convulsions can cause death or injury. A common form of generalized convulsive status epilepticus is of focal onset. The neuronal circuits activated during seizure spread from the hippocampus, a frequent site of seizure origin, to the bilateral motor cortex, which mediates convulsive seizures, have not been delineated.

DiI Perfusion as a Method for Vascular Visualization in Ambystoma mexicanum.

Perfusion techniques have been used for centuries to visualize the circulation of tissues. Axolotl (Ambystoma mexicanum) is a species of salamander that has emerged as an essential model for regeneration studies. Little is known about how revascularization occurs in the context of regeneration in these animals.