Distance-dependent increase in AMPA receptor number in the dendrites of adult hippocampal CA1 pyramidal neurons

The Schaffer collateral pathway provides hippocampal CA1 pyramidal cells wi th a fairly homogeneous excitatory synaptic input that is spread out across several hundred micrometers of their apical dendritic arborizations. A pro gressive increase in synaptic conductance, with distance from the soma, has been reported to reduce the location dependence that should result from th is arrangement. The excitatory synaptic contacts within this pathway primar ily use AMPA- and NMDA- type glutamate receptors. To investigate the underl ying mechanism of the increased distal excitatory postsynaptic conductance, we used outside-out patches and a fast application system to characterize the properties and distribution of synaptic glutamate receptors across the range of apical dendrites receiving Schaffer collateral input. We observed an approximately twofold increase in AMPA- mediated current amplitude (0.3- 0.6 nA) in the range of CA1 apical dendrites that receive a uniform density of Schaffer collateral input (similar to 100-250 mum from soma). NMDA-medi ated current amplitude, however, remained unchanged. We analyzed the curren t kinetics, agonist affinity, single-channel conductance, maximum open prob ability, and reversal potential of AMPA receptors and did not find any diff erences. Instead, the number of AMPA receptors present in our patches incre ased approximately twofold. These data suggest that an increase in the numb er of AMPA receptors present at distal synapses may play an important role in the distance-dependent scaling of Schaffer collateral synapses.