Electrophysiological analysis of synaptic plasticity in the denervated dentate gyrus

The molecular layer of the dentate gyrus undergoes considerable anatomically measurable changes after loss of its major excitatory afferents; perforant path fibers. The functional consequences of these changes are not known. This problem is compounded by an incomplete characterization of the pharmacology of normal perforant path/granule cell synaptic activity.; Responses to low frequency and paired-pulse stimulation of lateral and medial perforant fibers were recorded extracellularly from hippocampal slices from control rats and guinea pigs and rats with partial entorhinal lesions. In control guinea pig slices activation of muscarinic acetylcholine receptors by carbachol depressed medial but not lateral perforant path field potentials. In control rat slices, activation of gamma-aminobutyric acid (GABA) receptors by baclofen enhanced lateral perforant path field potentials. Paired-pulse potentiation was reduced by baclofen at long interstimulus intervals, enhanced by adenosine at short interstimulus intervals, and enhanced by scL-2-amino-4-phosphonobutanoate (scL-AP4) at all interstimulus intervals examined. Paired-pulse depression was reduced by scL-AP4 at short interstimulus intervals without a concommitant reduction of field potentials. This effect was mimicked by 1 scS,3 scR-1-aminocyclopentane-1,3-dicarboxylate, scDL-2-amino-3-phosphonopropionate and carbachol, but not GABA, muscarinic, or adenosine antagonists, or glutamate uptake or transient potassium current inhibitors. These results suggest that there are two components of the mechanisms underlying both paired-pulse potentiation and depression and that paired-pulse depression is not mediated by GABA-mediated inhibitory post-synaptic potentials, but may involve the phosphotidylinositol or cyclic AMP signalling systems.; In hippocampal slices prepared from rat two days post-lesion, medial perforant path field potentials were of small amplitude, opposite polarity and exhibited paired-pulse potentiation. By two weeks post-lesion medial perforant path field potentials recovered significantly in amplitude, polarity, and paired-pulse depression. Adenosine and carbachol reduced field potentials but not paired-pulse depression to a greater degree two weeks post-lesion. Field potentials tended to be more sensitive and paired-pulse depression less sensitive to scL-AP4. These results suggest that compensatory mechanisms triggered after partial entorhinal lesions are capable of significant recovery of perforant path/granule cell synaptic activity. The pharmacology of the recovered circuitry is also similar, except for greater sensitivity of field potentials to inhibition, especially by adenosine.