Abstracts

Rationale: Memory impairment is a common co-morbidity epilepsy that is associated malformations of cortical development. The reasons for memory impairment remain essentially unidentified. We studied spatial recognition memory performance and hippocampal CA1 synaptic plasticity in the in utero irradiation model of cortical dysplasia (CD).Methods: Embryonic day 17 rats were sham-exposed or exposed to 2.25 Gy external radiation. One-month-old rats (control, N = 13; irradiated, N = 12) were tested for spatial recognition memory using the place recognition task. Two weeks after behavioral testing, paired-pulse facilitation (PPF; control, N = 26; irradiated, N = 24) and long-term potentiation (LTP, induced by high frequency stimulation 100 Hz for 1 sec) or long-term depression (LTD, induction by low frequency stimulation 1 Hz for 900 sec; for both LTP and LTD, control, N =13; irradiated, N = 12) of the slope of fEPSP were studied in hippocampal slices (2 recordings/rat). For all comparisons significance was set at P < 0.05.Results: Behavioral assessments showed significantly impaired spatial recognition memory as evidenced by a significantly shorter time exploring novel locations and lower exploration ratios during the test phase in irradiated rats (both P < 0.01). Neurophysiological assessments showed that baseline synaptic transmission was significantly enhanced (as revealed by a left-shifted input/output curve), whereas PPF, LTP and LTD of the fEPSP slope at Schaffer collateral/commissural fiber-hippocampal CA1 synapses were significantly reduced in irradiated rats compared to the control. They were 1.733 0.059 (fEPSP slope in response to pulse 2/pulse 1), 157.6 8.5% and 78.2 2.5% of baseline fEPSP slope in controls and 1.225 0.037, 112.8 5.6 % and 95.6 2.6 % of baseline fEPSP slope in irradiated rats, respectively (all P< 0.01).Conclusions: This study documents impairment in hippocampus-based spatial recognition memory accompanied by reduced short-term and long-term synaptic plasticity in rats with CD. This information may be used to help design therapies to address this serious co-morbidity in the future.