title: Distinct AMPA-type glutamatergic synapses in developing rat CA1 hippocampus.
abstract: We assessed synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) properties during synaptogenesis to describe the development of individual glutamatergic synapses on rat hippocampal CA1 principal neurons. Pharmacologically isolated AMPAR-mediated glutamatergic synaptic currents [evoked by stimulation of the Schaffer Collateral pathway, excitatory postsynaptic currents (EPSCs)], had significantly greater inward-rectification at ages P5-7 compared with P8-18. These inward rectifying EPSCs demonstrated paired-pulse dependent unblocking at positive holding potentials, consistent with voltage-dependent internal polyamine block. Measurements of paired-pulse facilitation did not support altered presynaptic properties associated with inward rectification. Using asynchronous EPSCs (aEPSCs) to analyze populations of individual synapses, we found that quantal amplitudes (Q) increased across early postnatal development (P5-P18) and were directly modulated by increases in the number of activated receptors. Quantal AMPAR decay kinetics (aEPSC τ(decay)s) exhibited the highest coefficient of variation (CV) from P5 to 7 and became markedly less variable at P8-18. At P5-7, faster quantal kinetics coexisted with much slower kinetics; only slower quantal kinetics were found at P8-18. This supports diverse quantal synaptic properties limited to P5-7. Multivariate cluster analysis of Q, CV(τ decay), and median τ(decay) supported a segregation of neurons into two distinct age groups of P5-7 and P8-18, similar to the age-related segregation suggested by inward rectification. Taken together, these findings support synaptic, calcium permeable AMPARs at a subset of synapses onto CA1 pyramidal neurons exclusively at P5-7. These distinct synapses coexist with those sharing the properties of more mature synapses. These synapses disappear after P7 as activated receptor numbers increase with age.
authors.affiliation: University of Colorado Denver, Department of Pharmacology, Aurora, CO 80045, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Stubblefield
authors.forename: Tim A
authors.initials: TA
authors.lastname: Benke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA