Distinct AMPA - type glutamatergic synapses in developing rat CA 1 hippocampus 1

(246/250 words) 16 We assessed synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate 17 receptor (AMPAR) properties during synaptogenesis in order to describe the 18 development of individual glutamatergic synapses on rat hippocampal CA1 principal 19 neurons. Pharmacologically isolated AMPAR-mediated glutamatergic synaptic currents 20 (evoked by stimulation of the Schaffer Collateral pathway, EPSCs), had significantly 21 greater inward-rectification at ages P5-7 compared to P8-18. These inward rectifying 22 EPSCs demonstrated paired-pulse dependent unblocking at positive holding potentials, 23 consistent with voltage-dependent internal polyamine block. Measurements of paired24 pulse facilitation did not support altered presynaptic properties associated with inward 25 rectification. Using asynchronous EPSCs (aEPSCs) in order to analyze populations of 26 individual synapses, we found that quantal amplitudes (Q) increased across early 27 postnatal development (P5-P18) and were directly modulated by increases in the number 28 of activated receptors. Quantal AMPAR decay kinetics (aEPSC τdecays) exhibited the 29 highest coefficient of variation (CV) from P5-P7 and became markedly less variable at 30 P8-P18. At P5-7, faster quantal kinetics coexisted with much slower kinetics; only 31 slower quantal kinetics were found at P8-18. This supports diverse quantal synaptic 32 properties limited to P5-7. Multivariate cluster analysis of Q, CVτdecay, and median τdecay 33 supported a segregation of neurons into 2 distinct age groups of P5-7 and P8-18, similar 34 to the age-related segregation suggested by inward rectification. Taken together, these 35 findings support synaptic, calcium permeable AMPARs at a subset of synapses onto CA1 36 pyramidal neurons exclusively at P5-7. These distinct synapses coexist with those 37 sharing the properties of more mature synapses. These synapses disappear after P7 as 38 activated receptor numbers increase with age. 39