| Abstract No.: | C-B3071 |
| Country: | Canada |
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| Title: | DEVELOPMENT OF DENDRITIC SPINES AND SPONTANEOUS SYNAPTIC ACTIVITY IN THE MEDIAL PREFRONTAL CORTEX. |
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| Authors/Affiliations: | 1 John Armstrong *; 1 Jonathan Lai;
1 University of Guelph, Department of Biomedical Sciences, ON, Canada
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| Content: | The prefrontal cortex (PFC) is important for higher level cognitive functions. It is one of the last regions of the cortex to develop and seems to play a critical role in the pathophysiology of many neurological and psychiatric disorders including schizophrenia, autism and mental retardation. Surprisingly, very little is known about when synapses are formed in the PFC and how synapse formation coincides with changes in dendritic spine density and morphology. Objectives: In the following study we have used Golgi-Cox staining and whole-cell voltage clamp recordings of spontaneous AMPA-receptor mediated excitatory postsynaptic currents (EPSCs) to examine the time course of synaptogenesis in the medial prefrontal cortex (mPFC) of the mouse. Materials and Methods: Golgi-Cox staining was carried out on the brains of 2-26 day old male CD1 mice. Pyramidal cells in layers III and V of the mPFC were examined and spine density and length were measured on distal apical, proximal and basilar dendrites. Whole cell voltage clamp recordings were carried out in layer III and V pyramidal cells in acute mPFC slices prepared from 2-26 day old male CD1 mice. The frequency (interevent interval) and amplitude of AMPA-receptor mediated spontaneous EPSCs were recorded in 10µM bicuculline, 50µM picrotoxin both with and with out 1µM tetrodotoxin to monitor miniature EPSCs (mEPSCs) and polysynaptic bursts respectively. Results: Examination of Golgi-Cox stained neurons revealed very few differences in spine density and spine length between layer III and layer V pyramidal cells. However, spines in both layer III and layer V neurons were significantly denser at postnatal day 2 (PND2) on basilar dendrites and at PND 16 on the main apical dendrite (proximal - between 25-50% of its length) compared to all other time points. Analysis of spine length revealed that spines on layer III and layer V neurons were significantly longer at PND16 on basilar dendrites, PND 8 on distal apical dendrites and at PND16 on proximal dendrites compared to all other time points. Analysis of spontaneous AMPA-receptor mediated EPSCs revealed significantly more cells exhibiting polysynaptic burst activity at PND10-14 than any other time point. Significantly more polysynaptic bursts (per 10 minutes) were observed in cells recorded from PND10-14 slices, and these bursts were significantly longer in duration than bursts that occurred in cells taken from slices of younger or older animals. Analysis of the frequency of bursts and the interburst interval revealed a statistically significant longer time between bursts at PND10-14 than any of the other time points. Analysis of mEPSC frequency and amplitude is currently under way. Conclusion: An important change in dendritic spine length and spontaneous synaptic activity occurs in the mPFC during the 2nd week of postnatal development in the mouse.
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