title: Increased GABAergic inhibition in the midline thalamus affects signaling and seizure spread in the hippocampus-prefrontal cortex pathway.
abstract: OBJECTIVE
  The midline thalamus is an important component of the circuitry in limbic seizures, but it is unclear how synaptic modulation of the thalamus affects that circuitry. In this study, we wished to understand how synaptic modulation of the thalamus can affect interregional signaling and seizure spread in the limbic network.
  
  
  METHODS
  We examined the effect of γ-aminobutyric acid (GABA) modulation of the mediodorsal (MD) region of the thalamus on responses in the prefrontal cortex (PFC) by stimulation of the subiculum (SB). Muscimol, a GABA(A) agonist, was injected into the MD, and the effect on local responses to subiculum stimulation was examined. Evoked potentials were induced in the MD and the PFC by low-frequency stimulation of the SB, and seizures were generated in the subiculum by repeated 20-Hz stimulations. The effect of muscimol in the MD on the evoked potentials and seizures was measured.
  
  
  RESULTS
  Thalamic responses to stimulation of the subiculum were reduced in the presence of muscimol. Reduction of the amplitudes of evoked potentials in the MD resulted in an attenuation of the late, thalamic components of the responses in the PFC, as well as of seizure durations.
  
  
  CONCLUSIONS
  Activation of GABA(A) receptors in the midline thalamus not only causes changes within the thalamus, but it has broader effects on the limbic network. This work provides further evidence that synaptic modulation within the midline thalamus alters system excitability more broadly and reduces seizure activity.
authors.affiliation: Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Sloan
authors.forename: DeXing
authors.initials: D
authors.lastname: Zhang
authors.forename: Edward H
authors.initials: EH
authors.lastname: Bertram
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008032:Limbic System / Q000503:physiopathology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid