Information transmission in a constitutively active GABAergic synapse

Abstract

Short-term depression is a low pass filter of synaptic information that reduces and flattens synaptic information transfer at high presynaptic firing frequencies. This view questions the relevance of spontaneous high firing rates in some networks. In the indirect pathway of the basal ganglia, spontaneously active neurons in the globus pallidus (GP) form depressing inhibitory synapses in the basal ganglia output nuclei. Using numerical modeling and whole-cell recordings from single entopeduncular nucleus (EP) neurons in rat brain slices we investigated the contribution of the different firing rates of GP neurons to information transmission in the indirect pathway. Wholecell recordings showed significant variability in steady-state depression which decreased as stimulation frequency increased. Modeling predicted that this variability would translate into different postsynaptic noise levels during constitutive presynaptic activity. Our simulations further predicted that individual GP-EP synapses mediate gain control. However, when we consider integration of multiple inputs, the large range of GP firing rates would enable different modes of information transmission in which the magnitude and temporal features of postsynaptic modulation would change as a function of present and past firing rates of GP neurons. Finally, we predict that changes in dopamine levels can shift the action of GP neurons from rate coding to gain modulation. Our results thus demonstrate how short-term synaptic depression shapes information transmission in the basal ganglia in particular and via GABAergic synapses in general.\n\nSignificant statementSynapses displaying short-term depression are low-pass filters of synaptic input. Consequently, when presynaptic firing is high, little information passes to the postsynaptic neuron. However, many neurons fire at relatively high frequencies all the time. Are their synapses constantly silenced by depression? We tested this apparent contradiction in the indirect pathway of the basal ganglia, where neurons from the globus pallidus (GP) form constitutively active depressing synapses on basal ganglia output. We hypothesized that the different rates of ongoing activity underlie different modes of action for GP neurons. We show that the synaptic and structural properties of the indirect pathway map GP baseline frequencies to different postsynaptic signals, thus demonstrating how short-term synaptic depression shapes information transmission in the basal ganglia.