Subdivisions in the Multiple GABAergic Innervation of Granule Cells in the Dentate Gyrus of the Rat Hippocampus

Abstract The sources of GABAergic innervation to granule cells were studied to establish how the basic cortical circuit is implemented in the dentate gyrus. Five types of neuron having extensive local axons were recorded electrophysiologically in vitro and filled intracellularly with biocytin (Han et al. , 1993). They were processed for electron microscopy in order to reveal their synaptic organization and postsynaptic targets, and to test whether their terminals contained GABA. (1) The hilar cell, with axon terminals in the commissural and association pathway termination field (HICAP cell), formed Gray's type 2 (symmetrical) synapses with large proximal dendritic shafts ( n = 18), two‐thirds of which could be shown to emit spines, and with small dendritic branches ( n = 6). Other boutons of the HICAP neuron were found to make either Gray's type 1 (asymmetrical) synapses ( n = 4) or type 2 synapses ( n = 6) with dendritic spines. Using a highly sensitive silver‐intensified immunogold method for the postembedding visualization of GABA immunoreactivity, both the terminals and the dendrites of the HICAP cell were found to be immunopositive, whereas its postsynaptic targets were GABA‐immunonegative. The dendritic shafts of the HICAP cell received synapses from both GABA‐negative and GABA‐positive boutons; the dendritic spines which densely covered the main apical dendrite in the medial one‐third of the molecular layer received synapses from GABA‐negative boutons. (2) The hilar cell, with axon terminals distributed in conjunction with the perforant path termination field (HIPP cell), established type 2 synapses with distal dendritic shafts ( n = 17), most of which could be shown to emit spines, small‐calibre dendritic profiles ( n = 2) and dendritic spines ( n = 6), all showing characteristics of granule cell dendrites. The sparsely spiny dendrites of the HIPP cell were covered with many synaptic boutons on both their shafts and their spines. (3) The cell with soma in the molecular layer had an axon associated with the perforant path termination field (MOPP cell). This GABA‐immunoreactive cell made type 2 synapses exclusively on dendritic shafts ( n = 20), 60% of which could be shown to emit spines. The smooth dendrites of the MOPP cell were also restricted to the outer two‐thirds of the molecular layer, where they received both GABA‐negative and GABA‐positive synaptic inputs. (4) The extensive axonal arborization of the dentate basket cell terminated mainly on somata ( n = 26) and proximal dendrites ( n = 9) in the granule cell layer, and some boutons made synapses on somatic spines ( n = 6); all boutons established type 2 synapses. (5) The dentate axo‐axonic cell established type 2 synapses ( n = 14) exclusively on axon initial segments of granule cells in the granule cell layer, and on initial segments of presumed mossy cells in the hilus. The results demonstrate that granule cells receive inputs from the local circuit axons of at least five distinct types of dentate neuron terminating in mutually exclusive domains of the cell's surface in four out of five cases. Four of the cell types (HICAP cell, MOPP cell, basket cell, axo‐axonic cell) contain GABA, and the HIPP cell may also be inhibitory. The specific local inhibitory neurons terminating in conjunction with particular excitatory amino acid inputs to the granule cells (types 1 – 3) are in a position to interact selectively with the specific inputs on the same dendritic segment. This arrangement provides a possibility for the independent regulation of the gain and long‐term potentiation of separate excitatory inputs, through different sets of GABAergic local circuit neurons. The pairing of excitatory and inhibitory inputs may also provide a mechanism for the downward reseating of excitatory postsynaptic potentials, thereby extending their dynamic range.