Spontaneous Subthreshold Membrane Potential Fluctuations and Action Potential Variability of Rat Corticostriatal and Striatal Neurons In Vivo

Abstract

We measured the timing of spontaneous membrane potential fluctuations and action potentials of medial and lateral agranular corticostriatal and striatal neurons with the use of in vivo intracellular recordings in urethan-anesthetized rats. All neurons showed spontaneous subthreshold membrane potential shifts from 7 to 32 mV in amplitude, fluctuating between a hyperpolarized down state and depolarized up state. Action potentials arose only during the up state. The membrane potential state transitions showed a weak periodicity with a peak frequency near 1 Hz. The peak of the frequency spectra was broad in all neurons, indicating that the membrane potential fluctuations were not dominated by a single periodic function. At frequencies >1 Hz, the log of magnitude decreased linearly with the log of frequency in all neurons. No serial dependence was found for up and down state durations, or for the time between successive up or down state transitions, showing that the up and down state transitions are not due to superimposition of noisy inputs onto a single frequency. Monte Carlo simulations of stochastic synaptic inputs to a uniform finite cylinder showed that the Fourier spectra obtained for corticostriatal and striatal neurons are inconsistent with a Poisson-like synaptic input, demonstrating that the up state is not due to an increase in the strength of an unpatterned synaptic input. Frequency components arising from state transitions were separated from those arising from the smaller membrane potential fluctuations within each state. A larger proportion of the total signal was represented by the fluctuations within states, especially in the up state, than was predicted by the simulations. The individual state spectra did not correspond to those of random synaptic inputs, but reproduced the spectra of the up and down state transitions. This suggests that the process causing the state transitions and the process responsible for synaptic input may be the same. A high-frequency periodic component in the up states was found in the majority of the corticostriatal cells in the sample. The average size of the component was not different between neurons injected with QX-314 and control neurons. The high-frequency component was not seen in any of our sample of striatal cells. Corticostriatal and striatal neurons' coefficients of variation of interspike intervals ranged from 1.0 to 1.9. When interspike intervals including a down state were subtracted from the calculation, the coefficient of variation ranged from 0.4 to 1.1, indicating that a substantial proportion of spike interval variance was due to the subthreshold membrane potential fluctuations.

Interaction between neocortical and hippocampal networks via slow oscillations

“…Similar dynamics have been described in vitro in the presence of near normal Ca 2+ /high K + /low Mg 2+ , either spontaneously or in response to electrical stimulation of the cortex (Shu et al, 2003;Steriade et al, 1993b;Sanchez-Vives and McCormick, 2000), and during application of either mGluR agonists or muscarinic agonists (Beierlein et al, 2000). It has been suggested that both intrinsic cellular and network mechanisms are crucial for the slow oscillations (Wilson et al, 1990;Stern et al, 1997;Shu et al, 2003;Sanchez-Vives and McCormick, 2000) but the necessary and sufficient conditions that determine its frequency (the duration of UP and DOWN states) are still debated. The UP state is accompanied by the synchronous recruitment of numerous cells in the network and changes in input resistance Shu et al, 2003;Waters and Helmchen, 2006).…”

“…The DOWN state is associated with a positive polarity local field potential (LFP) in infragranular layers. Rhythmical shifts between DOWN and UP states have also been described in striatal (Wilson et al, 1990;Stern et al, 1997) and thalamic (Steriade et al, 1993b;Timofeev and Steriade, 1996;Hughes et al, 2002) neurons. Similar dynamics have been described in vitro in the presence of near normal Ca 2+ /high K + /low Mg 2+ , either spontaneously or in response to electrical stimulation of the cortex (Shu et al, 2003;Steriade et al, 1993b;Sanchez-Vives and McCormick, 2000), and during application of either mGluR agonists or muscarinic agonists (Beierlein et al, 2000).…”

Modeling functions of striatal dopamine modulation in learning and planning

“…Membrane potential fluctuations were usually recorded in anesthetized animals but also occur in awake animals with a less regular frequency (Wilson and Groves, 1981;Wilson, 1993). Increased activity of corticostriatal neurons seems to induce transitions to the up-state and to maintain the up-state (Wilson and Kawaguchi 1996;Stern et al 1997). In vivo stimulation of the cortex resets the phase of the oscillation (Katayama et al, 1980).…”

“…5B) (Wilson and Kawaguchi 1996;Stern et al 1997;Wickens and Wilson 1998). Membrane potential fluctuations were usually recorded in anesthetized animals but also occur in awake animals with a less regular frequency (Wilson and Groves, 1981;Wilson, 1993).…”

“…Likewise, dopamine long-term effects on corticostriatal transmission depend on the postsynaptic membrane potential . The membrane potential is influenced by synaptic inputs, by dopamine levels, and by rhythmic fluctuations of about 1 Hz between a depolarized up-state and a hyperpolarized down-state (Stern et al, 1997). We propose a model for striatal medium spiny neurons that mimics membrane potential fluctuations as well as dopamine effects on membrane properties and on corticostriatal transmission (section "Striatal Dopamine Modulation In Vivo").…”