Bilateral organization of parallel and serial pathways in the dentate gyrus demonstrated by current-source density analysis in the rat.

Abstract

1. Membrane currents evoked in the dentate gyrus (DG) by stimulation of afferent pathways from the entorhinal cortex (EC) and contralateral DG were examined by current-source density (CSD) analysis in urethan-anesthetized rats. Stimulation of each afferent pathway evoked membrane currents with distinct spatial and temporal organization in the DG. CSD and anatomic analysis revealed that afferent input from the EC activated the DG bilaterally through parallel and serial pathways. The analysis provided a detailed description of the location, timing, and relative amplitude of evoked monosynaptic and multisynaptic currents in the DG. 2. Orthodromic stimulation of the perforant path (PP) evoked a large ipsilateral excitatory postsynaptic current (iEPSC) at a latency of 2.5-4 ms in the middle and outer stratum moleculare (STM) of the DG, and a population spike that was generated by an excitatory inward current at a latency of 5-9 ms in the stratum granulosum. 3. A variable, low-amplitude ipsilateral inward current followed the population spike at a latency of 13-16 ms in the inner STM, which is the site of synaptic terminals of the associational and commissural pathways arising from neurons in the hilus of the DG. Orthodromic stimulation of the commissural pathway from the hilus of the contralateral DG also evoked an inward current in the inner STM at a latency of 2-6 ms, which was 40-60% of the amplitude of the monosynaptic iEPSC. 4. Orthodromic stimulation of the EC evoked a low-amplitude contralateral excitatory postsynaptic current (cEPSC) at a latency of 3-6 ms in the outer and middle STM of the contralateral DG, which was generated by monosynaptic transmission in the sparse crossed pathway from the EC. In contrast to the variable, low-amplitude inward current in the inner STM that followed the iEPSC, the cEPSC was consistently followed by a large inward current at a latency of 8-14 ms in the inner STM of the contralateral DG. 5. The large inward current in the inner STM of the contralateral DG was abolished by transection of the PP ipsilateral and rostral to the stimulating electrode, but was unaffected by transection of the PP at a similar location in the hemisphere contralateral to the stimulating electrode. These observations suggested that this current was most likely generated by a multisynaptic pathway involving the ipsilateral PP and the commissural pathway arising from the hilus of the DG. 6. In conclusion, efferents from the EC activated the DG bilaterally by parallel and serial pathways. Parallel monosynaptic pathways from the EC activated homologous distal segments of granule cell dendrites bilaterally, by a massive input to the ipsilateral DG and a sparse input to the contralateral DG. Sequential propagation from the EC through a multisynaptic pathway that included the commissural pathway from the hilus of the DG bilaterally activated the proximal segments of granule cell dendrites at longer latencies. The amplitude of the multisynaptic currents generated by serial pathways in the proximal dendrites varied inversely with the amplitudes of the monosynaptic currents evoked by parallel pathways in the distal dendrites. These observations may have implications for synaptic integration, associative properties, and information processing in the DG.