Investigation into the effects of neuropeptides on epileptiform activity in the hippocampus in vitro

Abstract

I used Electrophysiological recording techniques to investigate the effects of nociceptin (Noc) in various models of epileptiform activity, in acute hippocampal slices taken from adult rats. I subsequently looked at the effects of Noc in slices taken from an epileptic (EL) mouse model and in organotypic hippocampal slice cultures (OHSC’s). In some models I compare these effects to the action of Neuropeptide Y (NPY) as this is a well studied anti-convulsant neuropeptide.

I found that Noc caused a blockade of the bursting activity seen in the 10μM Biculculline (Bic) and 0 Mg⁺⁺ models of epileptiform activity. I also found that Noc did not cause a change in the bursting activity seen in the High K⁺ (8.5mM) or 100μM 4-Aminopyridine (4-AP) models.

When I looked at the Noc effects on the Bic and 0 Mg++ models in EL mice I found that Noc showed a greater reduction in bursting activity when applied to slices taken from ‘sensitised’ mice as compared to ‘non-sensitised’. I found that Noc showed no effects on synaptic transmission or paired-pulse inhibition in OHSC’s. The same result was seen with NPY. I showed through Western Blotting that the OP4, Y1, Y2 and Y5 receptors are present in OHSC’s. I then showed that Noc caused a reduction in bursting activity in the Bic model in OHSC’s and that no effect was seen when the experiment was repeated with NPY. I also experienced problems with the 4-AP model in OHSC’s and subsequently showed that 4-AP causes neuronal death in the CA1 sub-field of OHSC’s.

This data shows that targets of the OP4 receptor pathway could prove a useful experimental tool, and potential future anticonvulsant treatment.

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