Pentylenetetrazol-induced seizures are followed by a reduction in the multiunitary activity of hippocampal CA1 pyramidal neurons in adult rats.

Pentylenetetrazol (PTZ) blocks the inhibitory action of GABA, triggering a Glu-mediated hyperexcitation of the dendritic spines in hippocampal CA1 pyramidal neurons that leads to the generation of epileptiform seizures. The aim of this work was to determine the effect of PTZ on the electrical activity of the hippocampal pyramidal neurons in male rats. Bipolar electrodes were implanted stereotaxically in the right and left hippocampal CA1 fields of adults, and PTZ (65 mg/kg) was administered i.p. Simultaneous recordings of the field activity and the firing rate (multiunitary activity, MUA) were analyzed at 10, 20, and 30 min post-administration of PTZ. Only rats that presented tonic-clonic seizures during the first 1-5 min after PTZ treatment were included in the study. The recordings of the field activity were analyzed in 4 frequency bands. In both the right and left hippocampal CA1 fields, the relative power corresponding to the slow waves (4-7 Hz) increased, while in the bands 13-30 Hz and 31-50 Hz, it decreased at 10, 20, and 30 min post-PTZ. MUA recordings were analyzed at four levels. The highest levels corresponded to larger amplitudes of the action potentials in the pyramidal neurons. The firing rates of the PTZ-treated rats did not differ from baseline but presented a significant decrement at 10, 20, and 30 min post-PTZ. The decreased firing rate of the hippocampal CA1 pyramidal neurons after PTZ treatment could be associated with plastic changes of dendritic spines along with some microenvironmental adaptations at synaptic level, after neuronal PTZ-mediated hyperexcitation.

Pentylenetetrazol-induced seizures in adult rats are associated with plastic changes to the dendritic spines on hippocampal CA1 pyramidal neurons.

Epilepsy is a chronic neurobehavioral disorder whereby an imbalance between neurochemical excitation and inhibition at the synaptic level provokes seizures. Various experimental models have been used to study epilepsy, including that based on acute or chronic administration of Pentylenetetrazol (PTZ). In this study, a single PTZ dose (60 mg/kg) was administered to adult male rats and 30 min later, various neurobiological parameters were studied related to the transmission and modulation of excitatory impulses in pyramidal neurons of the hippocampal CA1 field. Rats experienced generalized seizures 1-3 min after PTZ administration, accompanied by elevated levels of Synaptophysin and Glutaminase. This response suggests presynaptic glutamate release is exacerbated to toxic levels, which eventually provokes neuronal death as witnessed by the higher levels of Caspase-3, TUNEL and GFAP. Similarly, the increase in PSD-95 suggests that viable dendritic spines are functional. Indeed, the increase in stubby and wide spines is likely related to de novo spinogenesis, and the regulation of neuronal excitability, which could represent a plastic response to the synaptic over-excitation. Furthermore, the increase in mushroom spines could be associated with the storage of cognitive information and the potentiation of thin spines until they are transformed into mushroom spines. However, the reduction in BDNF suggests that the activity of these spines would be down-regulated, may in part be responsible for the cognitive decline related to hippocampal function in patients with epilepsy.