Intra-hippocampal tonic inhibition influences formalin pain-induced pyramidal cell suppression, but not excitation in dorsal field CA1 of rat

It has been hypothesized that intra-hippocampal GABAergic inhibitory interneurons mediate formalin pain-induced suppression of dorsal hippocampal CA1 pyramidal cell discharge. The present study performed on anaesthetized rats tested the hypothesis by disrupting GABAergic mechanisms with intra-hippocampal administration of the GABAA receptor antagonist bicuculline methiodide, applied either dorsally into the pyramidal cell layer and stratum oriens (dorsal-bicuculline) or ventrally into the region of apical dendrites (ventral-bicuculline). It was found that ventral-, but not dorsal-bicuculline attenuated formalin-induced suppression of pyramidal cell extracellular discharge. The antagonism was selective in such a way that the excitation of pyramidal cell was unaffected. Interestingly, ventral-bicuculline strongly disinhibited CA1 pyramidal cells and shifted the distribution of their spontaneous discharge to values higher than the control group. However, dorsal-bicuculline disinhibited the local CA1 interneurons that were strongly excited on injection of formalin. Overall, the findings favour the notion that tonic GABAA receptor mechanisms located in the region of apical dendrites facilitate formalin-induced pyramidal cell suppression by masking the background excitatory drive impinging on the pyramidal cells. Interestingly, both the attenuation of formalin-induced inhibition and facilitation of basal discharge of CA1 pyramidal cells by ventral-bicuculline are similar to the effects seen previously with the destruction of medial septal cholinergic neurons. This convergence of effects strengthens the proposal that the network of medial septal cholinergic neurons and hippocampal GABAergic interneurons influence formalin pain-induced CA1 pyramidal cell suppression. In addition, the data point to a non-overlapping excitatory drive whose strength is unaffected by the inhibitory drive that underpins formalin suppression.