Abstract

During activated states, neocortical neurons receive intense synaptic background activity, which induces large-amplitude membrane potential fluctuations and a strong conductance in the membrane. However, little is known about the integrative properties of neurons during such high-conductance states. Here we investigated the integrative properties of neocortical pyramidal neurons under in vivo conditions simulated by computational models. We show that the presence of high-conductance fluctuations induces a stochastic state in which active dendrites are fast-conducting and have a different dynamics of initiation and forward-propagation of Na+-dependent spikes. Synaptic efficacy, quantified as the probability that a synaptic input specifically evokes a somatic spike, was roughly independent of the dendritic location of the synapse. Synaptic inputs evoked precisely timed responses (milliseconds), which also showed a reduced location dependence. This scheme was found to apply for a broad range of kinetics and density distributions of voltage-dependent conductances, as well as for different dendritic morphologies. Synaptic efficacies were, however, modulable by the balance of excitation and inhibition in background activity, for all synapses at once. Thus, models predict that the intense synaptic activity in vivo can confer advantageous computational properties to neocortical neurons: they can be set to an integrative mode which is stochastic, fast-conducting, and optimized to process synaptic inputs at high temporal resolution independently of their position in the dendrites. Some of these predictions can be tested experimentally.

Complementary Information and Material

1. NEURON demo files

NEURON demo files: ZIP (19 kByte)

This package contains all the mechanisms necessary to implement the models investigated in this paper, using the NEURON simulation environment (NEURON is freely available at www.neuron.yale.edu). The mechanisms included here are the voltage-dependent Na⁺, K⁺ and Ca²⁺ currents, as well as synaptic (AMPA, GABA_A) receptor types. Further instructions are provided in a README file, as well as comments in each file.

2. Movies

The computer animations illustrate the dynamics of spiking in soma and dendrites in a simulated neocortical layer VI pyramidal neuron. The somatodendritic distribution of membrane potential is shown by colors in three cases:

	Spontaneous activity in the active state (Vm fluctuations and spontaneous dendritic spikes). 70 ms activity are shown; Vm scale as in the cover picture; correlated background activity (Pearson correlation of 0.1).
	Initiation and propagation of dendritic spike in active state evoked by synaptic stimulation in the distal part of upper dendrite (stimulation amplitude of 4.8 nS, 2 stimulations are shown). A local dendritic spike is initiated, propagates reliable to the soma and initiates there a response. The Vm traces below are: green - dendrite an site of stimulation; red - soma; blue - axon initial segment (70 ms duration).
	Same as preceding case, but without background activity. The stimulation amplitude was in this case of 9.6 nS (2 stimulations shown), which inititates a local dendritic spike, which propagates only over limited distance and does not elicit a somatic response.

3. Journal cover page

PDF (1.1 MByte)