INTRASEPTAL MICROINFUSION OF MUSCIMOL - EFFECTS ON HIPPOCAMPAL-FORMATION THETA-FIELD ACTIVITY AND PHASIC THETA-ON CELL DISCHARGES

The effect of intraseptal microinfusions of the GABA-A agonist muscimo l on spontaneously occurring or hypothalamically induced hippocampal f ormation (HPC) theta field activity and the simultaneously occurring d ischarge properties of CA1 pyramidal and dentate granule layer phasic theta-ON cells, was investigated in urethane-anesthetized rats. The mi croinfusion of 5.0-12.5 nmol of muscimol into the medial septum/ verti cal limb of the diagonal band of Broca (MS/vDBB) resulted in a progres sive reduction (beginning 5 min postinfusion) in the power (amplitude) and finally the total loss of theta field activity. In contrast, thet a field frequency remained unaffected during the entire postinfusion p eriod that theta held activity was present. In the time immediately fo llowing the first 1-min intraseptal microinfusion of 5 nmol muscimol, (before changes in theta amplitude occurred) a brief period of increas ed phasic theta-ON cell excitability was noted. This was manifested as an increase in the number of discharges per rhythmic burst. Associate d with the progressive reduction of the amplitude of theta field activ ity, phasic theta-ON cell discharge rates progressively decreased for a period beginning 5 min postinfusion of 5 nmol muscimol. Despite the progressive decrease in the number of discharges and a noticeable redu ction in the degree of rhythmicity, phasic theta-ON cells maintained t heir preferred timing of discharges in relation to the phase of theta field activity, while the latter was present. Just prior to the comple te abolishment of theta field activity, phasic theta-ON cells ceased d ischarging. During the period when theta field activity was replaced b y low amplitude asynchronous activity, phasic theta-ON cells discharge d in bursts correlated with every occurence of sharp wave field activi ty. The results support the following conclusions: (1) the brief excit atory effect on HPC theta-ON cell discharges may be correlated pharmac ologically with an initial brief increase in HPC ACh turnover. The red uction of phasic theta-ON cell discharges and theta field activity may be correlated with the longer lasting reduction of HPC ACh turnover, controlled by MS/vDBB GABA-A inputs to MS/vDBB cholinergic septohippoc ampal neurons, possibly along with a direct inhibition of the GABAergi c septohippocampal projection; (2) the primary contribution of the MS/ vDBB nuclei, as a nodal point in the ascending brainstem HPC synchroni zing system, is the modulation of the amplitude of HPC formation theta field activity and secondarily to relay frequency-coded inputs from t he posterior hypothalamic region (posterior and supramammillary nuclei ); (3) HPC theta and sharp wave held activity represent functionally d istinct neural inputs to the same population of phasic theta-ON cells located in both the CA1 pyramidal and dentate granule cell layers. (C) 1996 Academic Press, Inc.