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Application of a NMDA Receptor Conductance in Rat Midbrain Dopaminergic Neurons Using the Dynamic Clamp Technique
Published on: December 21, 2010
Dynamical basis of irregular spiking in NMDA-driven prefrontal cortex neurons
Daniel Durstewitz1, Thomas Gabriel
1Centre for Theoretical and Computational Neuroscience, University of Plymouth, Plymouth, UK. daniel.durstewitz@plymouth.ac.uk
Cerebral Cortex (New York, N.Y. : 1991)
|June 3, 2006
Summary
Highly irregular neural firing in the prefrontal cortex (PFC), crucial for working memory, can be induced by N-Methyl-D-aspartic acid (NMDA) and dopamine D1 receptor agonists, suggesting complex nonlinear dynamics.
Area of Science:
- Neuroscience
- Computational Neuroscience
- Systems Neuroscience
Background:
- Slow N-Methyl-D-aspartic acid (NMDA) synaptic currents are hypothesized to drive elevated prefrontal cortex (PFC) firing rates during working memory.
- Neuronal firing during persistent activity in PFC is often characterized by high irregularity.
Purpose of the Study:
- To investigate the induction of highly irregular neuronal firing in the PFC.
- To explore the underlying mechanisms and computational implications of this irregular firing.
Main Methods:
- In vitro application of NMDA and dopamine D1 receptor agonists to adult PFC neurons.
- Analysis of interspike-interval (ISI) variability and subthreshold membrane potential distribution.
- Biophysical modeling of neuronal dynamics, including deterministic nonlinear processes.
Main Results:
- Combined NMDA and D1 receptor activation induced highly irregular firing in PFC neurons.
- Maximal ISI variability occurred during a transition in membrane potential distribution from unimodal to bimodal.
- Irregular firing exhibited predictability beyond noise-driven linear processes, consistent with nonlinear deterministic dynamics.
- Biophysical models reproduced these findings, highlighting a chaotic, near-bifurcation regime crucial for irregular dynamics.
Conclusions:
- NMDA receptor nonlinearity is critical for inducing irregular neuronal dynamics.
- These NMDA-induced irregular dynamics may play a significant role in working memory computations and neural coding.
- The findings suggest complex, potentially chaotic, nonlinear processes underlie persistent activity in the PFC.
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