The establishment of GABAergic and glutamatergic synapses on CA1 pyramidalneurons is sequential and correlates with the development of the apical dendrite

We have performed a morphofunctional analysis of CA1 pyramidal neurons at b irth to examine the sequence of formation of GABAergic and glutamatergic po stsynaptic currents (PSCs) and to determine their relation to the dendritic arborization of pyramidal neurons. We report that at birth pyramidal neuro ns are heterogeneous. Three stages of development can be identified: (1) th e majority of the neurons (80%) have small somata, an anlage of apical dend rite, and neither spontaneous nor evoked PSCs; (2) 10% of the neurons have a small apical dendrite restricted to the stratum radiatum and PSCs mediate d only by GABA(A) receptors; and (3) 10% of the neurons have an apical dend rite that reaches the stratum lacunosum moleculare and PSCs mediated both b y GABA(A) and glutamate receptors. These three groups of pyramidal neurons can be differentiated by their capacitance (C-m = 17.9 +/- 0.8; 30.2 +/- 1. 6; 43.2 +/- 3.0 pF, respectively). At birth, the synaptic markers synapsin- 1 and synaptophysin labeling are present in dendritic layers but not in the stratum pyramidale, suggesting that GABAergic peridendritic synapses are e stablished before perisomatic ones. The present observations demonstrate th at GABAergic and glutamatergic synapses are established sequentially with G ABAergic synapses being established first most likely on the apical dendrit es of the principal neurons. We propose that different sets of conditions a re required for the establishment of functional GABA and glutamate synapses , the latter necessitating more developed neurons that have apical dendrite s that reach the lacunosum moleculare region.