009-22 – Investigating hippocampal synaptic deficits in the sub-chronic phencyclidine rat model for schizophrenia

Background: Schizophrenia is a complex neuropsychiatric disorder characterised by three main symptom domains, namely positive, negative, and cognitive deficits. Recent evidence suggests that the cognitive impairments associated with schizophrenia (CIAS) are the main determinant of functional outcomes. However, to date, there is no licenced treatment for CIAS. N -methyl-D-aspartate receptor (NMDA) receptor antagonist rodent models are routinely used to model CIAS and provide a reliable model for investigating underlying mechanisms.
Methods: Animals received either phencyclidine (scPCP) 2 mg/kg or vehicle bi-daily for 7 days followed by a minimum 7 day washout period prior to behavioural testing (novel object recognition). Synaptic function in the CA1 region of the dorsal hippocampus was then assessed by acute electrophysiology under urethane anaesthesia in vivo. CA3-evoked field excitatory postsynaptic potential (fEPSP) in CA1 were analysed to investigate differences in synaptic connectivity and short/long-term synaptic plasticity.
Results: The scPCP group showed expected novel object recognition deficits in behavioural testing. Our electrophysiology data shows that whilst short-term plasticity (paired-pulse facilitation) was similar between vehicle and scPCP groups, synaptic connectivity (input-output function) was significantly decreased in the scPCP group. Early data from ongoing experiments show that: (a) both groups support long-term synaptic potentiation in CA1 following high-frequency stimulation; and (b) depotentiation of fEPSP slope and amplitude after LTP induction appears similar between groups, with both reversing towards the baseline. Full results and outcomes will be presented on the poster.
Conclusion: In summary, our data indicate that the well-established cognitive deficit in the scPCP rat model is accompanied by a complex change in hippocampal synaptic networks.