Regulation of the timing and pattern of action potential generation in rat subthalamic neurons in vitro by GABA-A IPSPs.

The regulation of activity in the subthalamic nucleus (STN) by GABAergic inhibition from the reciprocally connected globus pallidus (GP) plays an important role in normal movement and disorders of movement. To determine the precise manner in which GABAergic synaptic input, acting at A-type receptors, influences the firing of STN neurons, we recorded the response of STN neurons to GABA-A inhibitory postsynaptic potentials (IPSPs) that were evoked by supramaximal electrical stimulation of the internal capsule using the perforated-patch technique in slices at 37 degrees C. The mean equilibrium potential of the GABA-A IPSP (EGABA-A IPSP) was -79.4 +/- 7.0 mV. Single IPSPs disrupted the spontaneous oscillation that underlies rhythmic single-spike firing in STN neurons. As the magnitude of IPSPs increased, the effectiveness of prolonging the interspike interval was related more strongly to the phase of the oscillation at which the IPSP was evoked. Thus the largest IPSPs tended to reset the oscillatory cycle, whereas the smallest IPSPs tended to produce relatively phase-independent delays in firing. Multiple IPSPs were evoked at various frequencies and over different periods and their impact was studied on STN neurons held at different levels of polarization. Multiple IPSPs reduced and/or prevented action potential generation and/or produced sufficient hyperpolarization to activate a rebound depolarization, which generated a single spike or restored rhythmic spiking and/or generated a burst of activity. The pattern of IPSPs and the level of polarization of STN neurons were critical in determining the nature of the response. The duration of bursts varied from 20 ms to several hundred milliseconds, depending on the intrinsic rebound properties of the postsynaptic neuron. These data demonstrate that inhibitory input from the GP can produce a range of firing patterns in STN neurons, depending on the number and frequencies of IPSPs and the membrane properties and voltage of the postsynaptic neuron.

Hippocampal theta-related cellular activity in the superior colliculus of the urethane-anesthetized rat.

In the present study, 93 cells in the superior colliculus (SC) were recorded extracellularly during the simultaneous occurrence of spontaneous theta field activity, sensory-induced (tail pinch) theta field activity, and large amplitude irregular (LIA) field activity, recorded from an electrode located in the stratum moleculare of the hippocampal formation (HPC). The effect of the intravenous administration of atropine sulfate (ATSO4) was also tested on SC cellular activity. The field activities of theta and LIA were recorded from all layers of the SC and were found to be temporally coherent with the same activities recorded simultaneously from the HPC, during all conditions tested. By using the criteria of Colom and Bland (1987) for the classification of theta-related cells, 75 of 93 cells (81%) were found to be related to the generation of theta field activity in the HPC and 18 of 93 (19%) were nonrelated. All cells recorded discharged in a tonic, nonrhythmic pattern during the theta HPC field states. Of the 75 theta-related cells, 61 (81%) were classified as tonic theta-ON cells and 14 (19%) as tonic theta-OFF cells. Although these cell types were found in all three layers of the SC, the majority of tonic theta-ON cells were recorded in the intermediate layer, and the tonic theta-OFF cells were dispersed evenly between the intermediate layer and the deep layer of the SC. The intravenous administration of ATSO4 abolished theta field activity in the HPC and SC, and the theta-related increase in the discharge rate of all tonic theta-ON cells tested. However, the same treatment did not have any effect on the discharge properties of tonic theta-OFF cells. The same stimuli that resulted in the inhibition of the discharge rates of these cells (tail pinch and electrical stimulation of the PH) in the predrug condition did so after the administration of ATSO4.

Distribution and analysis of hippocampal theta-related cells in the pontine region of the urethane-anesthetized rat.

In the present study 99 cells were recorded in the pontine region of urethane-anesthetized rats during: (1) the spontaneous occurrence of hippocampal formation (HPC) theta field activity; (2) sensory-induced (tail pinch) theta field activity; and (3) large amplitude irregular field activity (LIA). Using the criteria of Colom and Bland (Brain Res 1997;422:277-286) for the classification of theta-related cells, 58/99 cells (59%) were involved with changes in activity related to the occurrence of HPC theta field activity, 24/99 (24%) were non-related, and 17/99 (17%) were related to the sensory input (tail pinch). All cells recorded discharged in a tonic, non-rhythmic pattern in relation to the HPC field activity occurring during the three conditions. Of the 58 theta-related cells, 52 (90%) were classified as tonic theta-ON cells and 6 (10%) as tonic theta-OFF cells. There were no clear regional differences in the distribution of cell types. Statistical analysis of the discharge rates of tonic theta-ON cells during spontaneously occurring theta and tail pinch-induced theta (tested on 48 cells) revealed that 22/48 (46%) of these cells discharged at significantly higher rates during the faster theta field frequencies associated with tail pinches while 26/48 (54%) tonic theta-ON cells did not change discharge rate between the spontaneously occurring theta and the tail pinch-induced theta states. In addition, the discharges of 11/52 (21%) tonic theta-ON cells exhibited weak to moderate correlations with the negative peak of HPC theta field activity recorded from the stratum moleculare of the dentate gyrus. Of the 17 cells related to the sensory stimulation (tail pinch), 12 (71%) cells increased discharge rate during the tail pinch and were classified as sensory activated, while 5 (29%) cells decreased discharge rate during the tail pinch and were classified as sensory inactivated. The results supported the following conclusions: (1) the main cells in the pontine region involved with changes in activity related to the occurrence of HPC theta field activity are tonic theta-ON cells and tonic theta-OFF cells; (2) a subpopulation of tonic theta-ON cells coded the increasing intensity of activation of the ascending brainstem HPC synchronizing pathways by an increase in discharge rate; and (3) a smaller population of cells in the rostral pontine region appeared to be related to sensory stimulation, independent of theta-related activity.