Patterns of activation in a monosynaptic cortical pathway: The perforant path input to the dentate area of the hippocampal formation

Summary1.In rabbits, anaesthetized with urethane/chloralose, stimulation with tungsten microelectrodes was employed to initiate a volley in the perforant path fibres which made en-passage contacts with the apical dendrites of dentate granule cells. The ensuing activation pattern was studied by recording the extracellular field potentials in the dentate area and the extra and intracellular responses of single granule cells.2.The afferent perforant path volley appeared as a small triphasic potential followed after 0.8 msec by a monosynaptic wave, which was maximally negative in the middle third of the molecular layer, corresponding to the region of the perforant path synapses on the granule cell dendrites. The wave became abruptly positive in the inner third of the molecular layer. After removal of the CA1, reversal occurred also in the outer third of the molecular layer, indicating an active synaptic sink restricted to the middle third of the dendritic region.3.A perforant path volley, propagating at a speed of about 3.3 m/sec, discharged granule cells lying in a horseshoeshaped segment of the dentate area. The dentate area is thus divided into a series of segments or lamellae by the perforant path input. Laterally, the perforant path fibres run through a bottle neck, deep to the angular bundle, before fanning out to enter the various segments of the dentate area of the dorsal hippocampus.4.A stimulus applied to the lateral region of the angular bundle activated the perforant path directly as well as indirectly. The indirect activation was presumably mediated by commissural fibres to the entorhinal area from which the perforant path originates.5.The negativity recorded extracellularly in the synaptic layer had the same onset as, but was phase advanced with respect to the intracellularly recorded EPSP. The monosynaptic extracellular negative wave was therefore interpreted as reflecting the synaptic current generating the intracellular EPSP and is termed the extracellular EPSP.6.When the perforant path volley was sufficiently large, a compound spike became superimposed on the extracellular EPSP. The spike was maximally negative in the granule cell body layer and positive in the outer dendritic region. Occasionally, multiple single cell discharges could be recorded in the granular layer. These unitary discharges always coincided in time with the compound spike and their number parallelled the size of the compound spike. The latter, therefore, reflects the number of nearly synchronously discharged cells and is termed the granule cell population spike.7.Typically, the granule cells discharged only once in response to a single perforant path volley. Subsequent discharges were blocked by inhibitory postsynaptic potentials, IPSPs. The postsynaptic excitatory response time varied between 5 msec and 1.4 msec depending on the size of the perforant path volley. A value of about 2 msec was most commonly observed in response to moderate or strong stimuli.8.The granule cells were discharged by a perforant path volley of increasing size only after a considerable growth of the extracellular EPSP had taken place. Apparently, the discharge requires summation of a large number of relatively small individual EPSPs. This may be a mode of synaptic activation characteristic of pathways with numerous boutons en-passage making contact with spines of profusely branching dendrites.