Persistent Changes in Spontaneous Firing of Purkinje Neurons Triggered by the Nitric Oxide Signaling Cascade

Smith, Spencer L.; Otis, Thomas S.

doi:10.1523/jneurosci.23-02-00367.2003

Cited by 73 publications

(61 citation statements)

References 39 publications

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“…The input-output function of Purkinje cells in response to synaptic stimulation Purkinje cells spike spontaneously in the absence of synaptic input (Häusser and Clark, 1997;Raman and Bean, 1997;Smith and Otis, 2003) and maintain high firing rates in vivo (Granit and Phillips, 1956;Eccles et al, 1967;Thach, 1968;Bell and Grimm, 1969;Armstrong and Rawson, 1979;Nitz and Tononi, 2002). We first examined how single EPSPs and IPSPs in isolation interact with spontaneous spiking in Purkinje cells in cerebellar slices.…”

Section: Resultsmentioning

confidence: 99%

Linking Synaptic Plasticity and Spike Output at Excitatory and Inhibitory Synapses onto Cerebellar Purkinje Cells

Mittmann¹,

Häusser²

2007

J. Neurosci.

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Understanding the relationship between synaptic plasticity and neuronal output is essential if we are to understand how plasticity is encoded in neural circuits. In the cerebellar cortex, motor learning is thought to be implemented by long-term depression (LTD) of excitatory parallel fiber (PF) to Purkinje cell synapses triggered by climbing fiber (CF) input. However, theories of motor learning generally neglect the contribution of plasticity of inhibitory inputs to Purkinje cells. Here we describe how CF-induced plasticity of both excitatory and inhibitory inputs is reflected in Purkinje cell spike output. We show that coactivation of the CF with PF input and interneuron input leads not only to LTD of PF synapses but also to comparable, "balanced" LTD of evoked inhibitory inputs. These two forms of plasticity have opposite effects on the spike output of Purkinje cells, with the number and timing of spikes sensitively reflecting the degree of plasticity. We used dynamic clamp to evaluate plasticity-induced changes in spike responses to sequences of excitation and feedforward inhibition of varied relative and absolute amplitude. Balanced LTD of both excitatory and inhibitory components decreased the net spike output of Purkinje cells only for inputs with small inhibitory components, whereas for inputs with a larger proportion of feedforward inhibition CF-triggered LTD resulted in an increase in the net spike output. Thus, the net effect of CF-triggered plasticity on Purkinje cell output depends on the balance of excitation and feedforward inhibition and can paradoxically increase cerebellar output, contrary to current theories of cerebellar motor learning.

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Section: Resultsmentioning

confidence: 99%

Linking Synaptic Plasticity and Spike Output at Excitatory and Inhibitory Synapses onto Cerebellar Purkinje Cells

Mittmann¹,

Häusser²

2007

J. Neurosci.

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“…With no current injection and with GABA A receptors blocked, Purkinje cells fired regular, spontaneous action potentials (Häusser and Clark, 1997;Smith and Otis, 2003) that were recorded through the somatic electrode ( Fig. 1 B, top panel).…”

Section: Resultsmentioning

confidence: 99%

Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons

2005

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In cerebellar Purkinje neurons, the reliability of propagation of high-frequency simple spikes and spikelets of complex spikes is likely to regulate inhibition of Purkinje target neurons. To test the extent to which a one-to-one correspondence exists between somatic and axonal spikes, we made dual somatic and axonal recordings from Purkinje neurons in mouse cerebellar slices. Somatic action potentials were recorded with a whole-cell pipette, and the corresponding axonal signals were recorded extracellularly with a loose-patch pipette. Propagation of spontaneous and evoked simple spikes was highly reliable. At somatic firing rates of ϳ200 spikes/sec, Ͻ10% of spikes failed to propagate, with failures becoming more frequent only at maximal somatic firing rates (ϳ260 spikes/sec). Complex spikes were elicited by climbing fiber stimulation, and their somatic waveforms were modulated by tonic current injection, as well as by paired stimulation to depress the underlying EPSCs. Across conditions, the mean number of propagating action potentials remained just above two spikes per climbing fiber stimulation, but the instantaneous frequency of the propagating spikes changed, from ϳ375 Hz during somatic hyperpolarizations that silenced spontaneous firing to ϳ150 Hz during spontaneous activity. The probability of propagation of individual spikelets could be described quantitatively as a saturating function of spikelet amplitude, rate of rise, or preceding interspike interval. The results suggest that ion channels of Purkinje axons are adapted to produce extremely short refractory periods and that brief bursts of forward-propagating action potentials generated by complex spikes may contribute transiently to inhibition of postsynaptic neurons.

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“…On average, their basal firing rates are ϳ40 Hz, but rates vary greatly between individual cells in vivo (Granit and Phillips, 1956;Armstrong and Rawson, 1979). The rate of spontaneous firing of Purkinje neurons is plastic and depends on the history of parallel fiber and climbing fiber activity (Smith and Otis, 2003;Cerminara and Rawson, 2004). Upregulation and downregulation of firing rates provides bidirectional inhibitory control of their target neurons in the deep cerebellar nuclei.…”

Section: Functional Implicationsmentioning

confidence: 99%

“…Spontaneous (intrinsic) spiking drives oscillatory or synchronous network behavior and is subject to activity-dependent plasticity that, on a slow timescale, regulates the intrinsic spike rate (Nelson et al, 2003;Smith and Otis, 2003). Purkinje neurons fire at an unusually high spontaneous frequency of ϳ40 Hz in vivo (Granit and Phillips, 1956;Armstrong and Rawson, 1979) and at similar frequencies in slice preparations (at physiological temperature) with synaptic inputs blocked (Llinas and Sugimori, 1980;Häusser and Clark, 1997).…”

Section: Introductionmentioning

confidence: 99%

Interaction of Kv3 Potassium Channels and Resurgent Sodium Current Influences the Rate of Spontaneous Firing of Purkinje Neurons

Akemann¹,

Knöpfel²

2006

J. Neurosci.

119

125

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Purkinje neurons spontaneously generate action potentials in the absence of synaptic drive and thereby exert a tonic, yet plastic, input to their target cells in the deep cerebellar nuclei. Purkinje neurons express two ionic currents with biophysical properties that are specialized for high-frequency firing: resurgent sodium currents and potassium currents mediated by Kv3.3. How these ionic currents determine the intrinsic activity of Purkinje neurons has only partially been understood. Purkinje neurons from mutant mice lacking Kv3.3 have a reduced rate of spontaneous firing. Dynamic-clamp recordings demonstrated that normal firing rates are rescued by inserting artificial Kv3 currents into Kv3.3 knock-out Purkinje neurons. Numerical simulations indicated that Kv3.3 increases the spontaneous firing rate via cooperation with resurgent sodium currents. We conclude that the rate of spontaneous action potential firing of Purkinje neurons is controlled by the interaction of Kv3.3 potassium currents and resurgent sodium currents.

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Persistent Changes in Spontaneous Firing of Purkinje Neurons Triggered by the Nitric Oxide Signaling Cascade

Cited by 73 publications

References 39 publications

Linking Synaptic Plasticity and Spike Output at Excitatory and Inhibitory Synapses onto Cerebellar Purkinje Cells

Linking Synaptic Plasticity and Spike Output at Excitatory and Inhibitory Synapses onto Cerebellar Purkinje Cells

Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons

Interaction of Kv3 Potassium Channels and Resurgent Sodium Current Influences the Rate of Spontaneous Firing of Purkinje Neurons

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