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Post weaning isolation-reared rats show deficits in learning and memory, which are also seen in many psychiatric disorders like schizophrenia. The present study utilized behavioral and electrophysiological tests to further characterize cognitive disorders in this rat model, and to explore possible neurobiological mechanisms associated with them. Isolation rearing was performed in male Wistar rats from weaning for 8 weeks. Spatial memory and reversal learning were assessed using Morris water maze (MWM); synaptic plasticity was assessed by recording long-term potentiation (LTP) from thalamus to prefrontal cortex; and potassium ion channel currents were tested using the cerebrospinal fluid (CSF) of different groups in hippocampal slices by patch clamp. The results of MWM showed that isolation-reared rats performed worse in probe trials and memory retention tests. The LTP tests showed that the prefrontal cortical postsynaptic potential slopes were significantly lower in isolated rats than group housed ones. The patch clamp recording showed that the amplitudes of hippocampal voltage-dependent transient outward K + currents ( I A ) were enhanced, and the steady inactivation curve of I A was shifted towards positive potential by CSF of isolated rats. These data suggested that isolation rearing can impair the spatial cognition of rats, with the possible mechanisms of affecting prefrontal cortical synaptic plasticity and hippocampal potassium ion channel currents.