title: Opposing alterations in excitation and inhibition of layer 5 medial prefrontal cortex pyramidal neurons following neonatal ventral hippocampal lesion.
abstract: Cognitive abnormalities in schizophrenia reflect deficits in prefrontal cortical function, which could be related to attrition of dendritic structures of prefrontal cortical neurons. Schizophrenia-related prefrontal deficits have been modeled in postpubertal neonatal ventral hippocampal lesioned (NVHL) rats, which displayed a loss of dendritic complexity and spines in layer 3 pyramidal neurons in the medial prefrontal cortex (mPFC). The influence of dendritic attrition on synaptic function and neuronal excitability in the mPFC remains poorly understood. Here, we performed electrophysiological recordings of layer 5 mPFC pyramidal neurons from postpubertal (postnatal 40-60 days) NVHL rats and sham-operated controls. We found that the dendritic length, complexity, and spine density of neurobiotin-labeled layer 5 mPFC pyramidal neurons in NVHL rats were significantly lower than those in sham-operated rats. However, the excitability of layer 5 mPFC pyramidal neurons remained unchanged after NVHL. We found no significant changes in the expression of vesicular glutamate and γ-aminobutyric acid transporters after NVHL. Intriguingly, NVHL increased the amplitude of action potential-independent miniature excitatory postsynaptic currents and decreased the frequency of miniature inhibitory postsynaptic currents. These opposing alterations in excitatory and inhibitory synapses, possibly shifting basal synaptic activity toward increased excitation, could be cellular substrates for mPFC functional deficits reported in NVHL rats.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Ryan
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Bhardwaj
authors.forename: Yiu C
authors.initials: YC
authors.lastname: Tse
authors.forename: Lalit K
authors.initials: LK
authors.lastname: Srivastava
authors.forename: Tak Pan
authors.initials: TP
authors.lastname: Wong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D009433:Neural Inhibition; D017397:Prefrontal Cortex / Q000503:physiopathology*; D017966:Pyramidal Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000503:physiopathology*; D009435:Synaptic Transmission