ADRENERGIC MODULATION OF HILAR NEURON ACTIVITY AND GRANULE CELL-INHIBITION IN THE GUINEA-PIG HIPPOCAMPAL SLICE

To study the effects of norepinephrine on synaptic inhibition in the d entate gyrus, intracellular recordings were made from hilar neurons in the guinea-pig hippocampal slice. The effects of norepinephrine on hi lar neurons were compared with changes in the frequency of spontaneous inhibitory postsynaptic potentials recorded from granule cells. Hilar neurons comprised two electrophysiologically distinct groups: type I hilar neurons displayed a pronounced single spike afterhyperpolarizati on and little spike frequency accommodation, type II hilar neurons had small afterhyperpolarizations and pronounced spike frequency accommod ation. The majority of recordings were from type I hilar neurons which are presumably inhibitory to granule cells. In most instances, effect s of norepinephrine (2-10 mu M) on hilar neurons could be mimicked by the beta-adrenergic agonist isoproterenol (0.1-1 mu M). Isoproterenol induced a slight depolarization, blocked a slow afterhyperpolarization and, in type II neurons, reduced spike frequency accommodation. These effects were associated with an increase in the spontaneous discharge rate and an enhancement of spontaneous excitatory and inhibitory post synaptic potentials. In accordance, isoproterenol and norepinephrine i ncreased the frequency of inhibitory postsynaptic potentials in granul e cells. In the presence of the non-N-methyl-D-aspartate receptor anta gonist 6-cyano-7-nitroquinoxaline-2,3-dione and the N-methyl-D-asparta te receptor antagonist CGP 37849, isoproterenol and norepinephrine als o increased the frequency of Cl--dependent inhibitory postsynaptic pot entials in granule cells, Under this experimental condition, however, norepinephrine reduced the discharge rate of type I hilar neurons thro ugh an effect on alpha-receptors. In the presence of GABA(A) receptor blockers, norepinephrine increased the frequency of spontaneously occu rring K+-dependent inhibitory postsynaptic potentials in granule cells . Accordingly, the frequency of burst discharges in type I hilar neuro ns was increased. We suggest that the discrepancy in the effect of nor epinephrine on the discharge rate of presumed inhibitory hilar neurons and the frequency of Cl--dependent inhibitory postsynaptic potentials in granule cells results from a direct effect of norepinephrine on GA BAergic terminals because norepinephrine also enhanced the frequency o f tetrodotoxin-resistant inhibitory postsynaptic potentials in granule cells. Thus, the net effect of synaptically released. norepinephrine on synaptic inhibition in the dentate gyrus will be determined by oppo sing actions of alpha- versus beta-receptor stimulation at the synapse on hilar neurons.