Septal GABAergic neurons are selectively vulnerable to pilocarpine-induced status epilepticus and chronic spontaneous seizures

Neuroscience. 2006 Oct 27;142(3):871-83. doi: 10.1016/j.neuroscience.2006.06.057. Epub 2006 Aug 24.


The septal region of the basal forebrain plays a critical role modulating hippocampal excitability and functional states. Septal circuits may also play a role in controlling abnormal hippocampal hyperexcitability in epilepsy. Both lateral and medial septal neurons are targets of hippocampal axons. Since the hippocampus is an important epileptogenic area in temporal lobe epilepsy, we hypothesize that excessive excitatory output will promote sustained neurodegeneration of septal region neurons. Pilocarpine-induced status epilepticus (SE) was chosen as a model to generate chronic epileptic animals. To determine whether septal neuronal populations are affected by hippocampal seizures, immunohistochemical assays were performed in brain sections obtained from age-matched control, latent period (7 days post-SE) and chronically epileptic (more than one month post-SE survival) rats. An anti-NeuN (neuronal nuclei) antibody was used to study total neuronal numbers. Anti-ChAT (choline acetyltransferase), anti-GAD (glutamic acid decarboxylase) isoenzymes (65 and 67), and anti-glutamate antibodies were used to reveal cholinergic, GABAergic and glutamatergic neurons, respectively. Our results revealed a significant atrophy of medial and lateral septal areas in all chronically epileptic rats. Overall neuronal density in the septum (medial and lateral septum), assessed by NeuN immunoreactivity, was significantly reduced by approximately 40% in chronically epileptic rats. The lessening of neuronal numbers in both regions was mainly due to the loss of GABAergic neurons (80-97% reduction in medial and lateral septum). In contrast, populations of cholinergic and glutamatergic neurons were spared. Overall, these data indicate that septal GABAergic neurons are selectively vulnerable to hippocampal hyperexcitability, and suggest that the processing of information in septohippocampal networks may be altered in chronic epilepsy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Cell Survival
  • Disease Models, Animal
  • Fluoresceins
  • Glutamate Decarboxylase
  • Immunohistochemistry / methods
  • Male
  • Nerve Degeneration / etiology
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Organic Chemicals / metabolism
  • Pilocarpine
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / complications
  • Seizures / pathology*
  • Septum of Brain / pathology*
  • Status Epilepticus / chemically induced
  • Status Epilepticus / complications
  • Status Epilepticus / pathology*
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism*


  • Fluoresceins
  • Nerve Tissue Proteins
  • Organic Chemicals
  • fluoro jade
  • Pilocarpine
  • gamma-Aminobutyric Acid
  • Glutamate Decarboxylase