Pathway-specific inhibition of critical projections from the mediodorsal thalamus to the frontal cortex controls kindled seizures

Wicker, Evan; Hyder, Safwan K; Forcelli, Patrick A.

doi:10.1016/j.pneurobio.2022.102286

Cited by 6 publications

(5 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Through the application of chemogenetic methodologies, circuits such as the nigra-parafascicular disinhibitory circuit, which regulates seizures in TLE, and the dHPC dorsal lateral septum circuit that impairs risk assessment behavior, have been identified and evaluated (Chen et al 2020 ; Cao et al 2022 ). Projections from the mediodorsal nucleus to the prelimbic cortex have also been implicated in the propagation of amygdala-kindled seizures (Wicker et al 2022 ). An increasing number of studies are leveraging chemogenetics for the specific activation and inhibition of neurons associated with particular circuits, thus assessing the impact of chemogenetic interventions on epileptic activity (Berglind et al 2018 ).…”

Section: Chemogeneticsmentioning

confidence: 99%

Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research

Xiao,

Li,

Kong

et al. 2024

Cell Mol Neurobiol

View full text Add to dashboard Cite

Epilepsy, a prevalent neurological disorder characterized by high morbidity, frequent recurrence, and potential drug resistance, profoundly affects millions of people globally. Understanding the microscopic mechanisms underlying seizures is crucial for effective epilepsy treatment, and a thorough understanding of the intricate neural circuits underlying epilepsy is vital for the development of targeted therapies and the enhancement of clinical outcomes. This review begins with an exploration of the historical evolution of techniques used in studying neural circuits related to epilepsy. It then provides an extensive overview of diverse techniques employed in this domain, discussing their fundamental principles, strengths, limitations, as well as their application. Additionally, the synthesis of multiple techniques to unveil the complexity of neural circuits is summarized. Finally, this review also presents targeted drug therapies associated with epileptic neural circuits. By providing a critical assessment of methodologies used in the study of epileptic neural circuits, this review seeks to enhance the understanding of these techniques, stimulate innovative approaches for unraveling epilepsy's complexities, and ultimately facilitate improved treatment and clinical translation for epilepsy. Graphical Abstract

show abstract

Section: Chemogeneticsmentioning

confidence: 99%

Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research

Xiao,

Li,

Kong

et al. 2024

Cell Mol Neurobiol

View full text Add to dashboard Cite

show abstract

“…For instance, activation of circuits projecting from the cerebellar parietal nucleus (FN) to the centrolateral thalamic nucleus (CL) exerts inhibitory effects on seizures, whereas regulation of circuits projecting to the SC or medullary reticular region (MdV) does not impact epileptic activity [14]. In the amygdala-kindled model [72], chemogenetic or optogenetic inhibition of glutamatergic projections from the basolateral amygdala nucleus (BLA) to the medial thalamic nucleus (MD) eliminated epileptic behavior and epileptiform electrical emission. Similarly, chemogenetic inhibition of MD projections to the anterior limbic cortex (medial prefrontal cortex) effectively abolished epileptic seizures.…”

Section: The Diverse Roles Of Different Glutamatergic Collaterals In ...mentioning

confidence: 99%

A review of cell-type specific circuit mechanisms underlying epilepsy

Zhao,

Ding,

et al. 2024

Acta Epileptologica

View full text Add to dashboard Cite

Epilepsy is a prevalent neurological disorder, yet its underlying mechanisms remain incompletely understood. Accumulated studies have indicated that epilepsy is characterized by abnormal neural circuits. Understanding the circuit mechanisms is crucial for comprehending the pathogenesis of epilepsy. With advances in tracing and modulating tools for neural circuits, some epileptic circuits have been uncovered. This comprehensive review focuses on the circuit mechanisms underlying epilepsy in various neuronal subtypes, elucidating their distinct roles. Epileptic seizures are primarily characterized by the hyperactivity of glutamatergic neurons and inhibition of GABAergic neurons. However, specific activated GABAergic neurons and suppressed glutamatergic neurons exacerbate epilepsy through preferentially regulating the activity of GABAergic neurons within epileptic circuits. Distinct subtypes of GABAergic neurons contribute differently to epileptic activities, potentially due to their diverse connection patterns. Moreover, identical GABAergic neurons may assume distinct roles in different stages of epilepsy. Both GABAergic neurons and glutamatergic neurons with long-range projecting fibers innervate multiple nuclei; nevertheless, not all of these circuits contribute to epileptic activities. Epileptic circuits originating from the same nuclei may display diverse contributions to epileptic activities, and certain glutamatergic circuits from the same nuclei may even exert opposing effects on epilepsy. Neuromodulatory neurons, including cholinergic, serotonergic, dopaminergic, and noradrenergic neurons, are also implicated in epilepsy, although the underlying circuit mechanisms remain poorly understood. These studies suggest that epileptic nuclei establish intricate connections through cell-type-specific circuits and play pivotal roles in epilepsy. However, there are still limitations in knowledge and methods, and further understanding of epileptic circuits is crucial, particularly in the context of refractory epilepsy.

show abstract

“…In the group of rats with cannulae aimed at the mPFC, a volume of 0.3 µl was infused into the mPFC in each hemisphere. Clozapine-N-oxide (CNO) hydrochloride (ChemSpecial, NC) was dissolved in sterile saline to make a 2.5 mM solution of CNO (Wicker et al 2022). A volume of 0.3 µl was infused into the either the RE or mPFC in each hemisphere.…”

Section: Drugsmentioning

confidence: 99%

Medial prefrontal cortex and nucleus reuniens are critical for working memory in an operant delayed nonmatch task

Ciacciarelli,

Dunn,

Gohar

et al. 2024

Preprint

View full text Add to dashboard Cite

Working memory refers to the temporary retention of a small amount of information used in the execution of a cognitive task. The prefrontal cortex and its connections with thalamic subregions are thought to mediate specific aspects of working memory, including engaging with the hippocampus to mediate memory retrieval. We used an operant delayed-non match to position task, which does not require the hippocampus, to determine roles of the rodent medial prefrontal cortex (mPFC), the nucleus reuniens thalamic region (RE), and their connection. We found that transient inactivation of the mPFC and RE using the GABA-A agonist muscimol led to a delay-independent reduction in behavioral performance in the delayed non-match to position paradigm. Critically, we used a chemogenetic approach to determine the directionality of the necessary circuitry for behavioral performance reliant on working memory. Specifically, when we targeted mPFC neurons that project to the RE (mPFC-RE) we found a delay- independent reduction in the delayed non-match to position task, but not when we targeted RE neurons that project to the mPFC (RE-mPFC). Our results suggest a broader role for the mPFC-RE circuit in mediating working memory beyond the connection with the hippocampus.

show abstract

Pathway-specific inhibition of critical projections from the mediodorsal thalamus to the frontal cortex controls kindled seizures

Cited by 6 publications

References 107 publications

Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research

Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research

A review of cell-type specific circuit mechanisms underlying epilepsy

Medial prefrontal cortex and nucleus reuniens are critical for working memory in an operant delayed nonmatch task

Contact Info

Product

Resources

About