Effects of cobalt and bicuculline on focal microstimulation of rat pallidal neurons in vivo

BackgroundDeep brain stimulation (DBS) administered in the basal ganglia is an effective therapy for movement disorders; however, the mechanism(s) of action remain poorly understood.ObjectiveBecause high-frequency electrical stimulation (HFS) preferentially activates fibers, one hypothesis of DBS action is that local release of transmitters from axon terminals underlies the inhibitory effects on spontaneous spiking observed in human intraoperative recordings. We hypothesize that blocking presynaptic release of transmitters will reduce any stimulation-induced effect and blocking of postsynaptic GABA receptors will reduce the inhibitory effect of HFS.MethodsWe recorded neuronal responses after short HFS trains (2-37 μA, 0.5 seconds, 300 Hz) delivered through the recording electrode or via an adjacent electrode in 42 single globus pallidus (GP) units of anesthetized rats before and after injection of the synaptic blockers cobalt chloride (100 mM) and bicuculline methiodide (2 μg/μL).ResultsResponses to HFS trains were mainly transient (∼350 milliseconds) inhibition of firing, but a late response (∼1-2 seconds) and rebound burst were also found. Excitation was observed in 4 of 43 neurons studied. Neurons with transient inhibition had the response attenuated by 47% after injection of either synaptic blocker, in part supporting the local gamma-aminobutyric acid release hypothesis. Bicuculline methiodide and cobalt attenuated the late response as well as the rebound burst response, but the late inhibitory response was increased by bicuculline methiodide in one case. HFS-induced excitatory responses were not altered by synaptic blockers suggesting direct stimulation of postsynaptic elements of GP neurons.ConclusionsThe results indicate HFS induces the local inhibition of ongoing activity of the somal region of GP neurons as well as the stimulation of axons and active dendrites. These observations serve to shed light on the mechanism(s) of DBS.