Figure 1.

Spontaneous firing, depolarization block and inhibition in cerebellar nuclear cells. (a) Spontaneous firing in a cerebellar nuclear cell isolated from the mouse cerebellum, in quasi-physiological extracellular and intracellular solutions (control). With voltage-gated Na⁺ channels blocked by TTX, the same cell rests at −47 mV (TTX). This depolarized resting membrane potential in TTX depends slightly on Ca²⁺ flux because the cell hyperpolarizes to −54 mV when the 2 mM Ca²⁺ in the bath is replaced with 2 mM Co²⁺ (Co²⁺TTX). When 155 mM Na⁺ in the control solution is reduced to 6 mM Na⁺ (6 Na⁺+TTX; equimolar substitution with N-methyl-D-glucamine⁺, 2 Ca²⁺ present), the membrane hyperpolarizes strongly to −74 mV. (b) Group data for resting membrane potential (RMP) in TTX for nine cells treated as in (a) (open symbols). Mean RMP (filled symbols) was −40 ± 2 mV in 155 mM Na⁺ (control solutions) and −61 ± 3 mV in 6 mM Na⁺. These data support the idea that a TTX-insensitive tonic cation current brings cerebellar nuclear cells above threshold. (a) and (b) are modified, with permission, from Ref. [9]. (c) A recording from a cerebellar nuclear neuron in a cerebellar slice from mouse with quasi-physiological solutions (35°C). The neuron was originally firing spontaneously (not shown), but it depolarized to produce the oscillatory behavior evident at the beginning of the trace. A 250 ms stimulation of mossy fiber excitatory afferents at 100 Hz (EPSPs) drives the cell further into depolarization block. A 150 ms stimulation of Purkinje axons at 100 Hz (IPSPs) hyperpolarizes the cell to a voltage near −60 mV. Spontaneous firing resumes after the train, illustrating that synaptic inhibition can restore the activity of cerebellar nuclear neurons that have entered depolarization block (J.R.P. and I.M.R., unpublished; recording conditions as in Ref. [67]).