Fos induction in subtypes of cerebrocortical neurons following single picrotoxin-induced seizures

In adult rats single seizures of varying behavioural severities were caused by slow, systemic infusion of picrotoxin, an antagonist of the Cl^- channel at the GABA(A) receptor. We used a double labelling immunohistochemical method to define the subclasses of neurons that contained Fos protein following seizures. In four cortical regions (piriform, entorhinal, motor and sensory) neuronal subclasses were defined with antibodies against the calcium-binding proteins calbindin D-28 K, parvalbumin and calretinin (aspiny neurons), and neurofilament protein (spiny neurons). The remaining spiny neuron lation was estimated by subtraction of defined subclasses from total neuronal numbers determined from Nissl stain. After seizures, most of the calbindin D-28 K immunoreactive interneurons (> 80%) and many of the unlabelled spiny neurons (60-80%) were Fos positive. Co-localisation of Fos was found in about 30% of parvalbumin, calretinin and neurofilament protein immunoreactive neurons. Paradoxically, mild seizures were associated with induction of Fos in up to 80% of cortical cells and more severe seizures with 60%, the difference being due to different levels of Fos induction in spiny neurons. These results also demonstrate that seizures induce Fos predominantly in excitatory cortical neurons.