Corticohippocampal circuit dysfunction in epilepsy

The role of subcortical neuromodulatory networks in seizures

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While cortical and limbic regions are known to be highly susceptible to seizures, converging evidence suggests that subcortical neuromodulatory networks may regulate when and how seizures start and propagate. Subcortical neuromodulatory neurons are clustered into small nuclei and send widespread projections throughout the central nervous system. They profoundly regulate the excitability of downstream targets and thereby modulate brain activity on a large scale. We are determining how seizures hijack subcortical neuromodulatory networks, and whether those networks can in turn be harnessed to prevent or curtail seizures.

  • How do subcortical neuromodulatory neurons endogenously respond to seizures?
  • What is the consequence of exogenously manipulating these neurons prior to or at seizure onset?

Corticohippocampal circuit dysfunction in epilepsy

Neuromodulatory networks in epilepsy

The impact of chronic epilepsy on neuromodulatory networks

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Although epilepsy is defined by recurrent seizures, its comorbid disorders – of attention, sleep mood, and cognition – are highly prevalent and often devastating to patients. Subcortical neuromodulatory networks are chronically impaired in epilepsy, which may contribute to these comorbidities, but a mechanistic link between seizures and chronic network dysfunction is lacking.

  • Are the intrinsic physiologic properties of neuromodulatory neurons altered in epilepsy? Is this exacerbated by recurrent seizures?
  • Does the pathologic hyperactivity in epilepsy trigger activity-dependent changes in neurotransmitter expression within neuromodulatory neurons?
  • What are the circuit-level consequences of the above?

Neuromodulatory networks in epilepsy