Chloride dynamics alter the input-output properties of neurons
Fig 2
The relative amounts of inhibitory and excitatory drive produce spatial variations in neuronal chloride concentration.
(A) Top, schematic depicting the model with an axon, soma, short thick ‘proximal’ dendrite connected to a long thin ‘distal’ dendrite. Both excitatory (red) and inhibitory (blue) synaptic input were evenly distributed across the distal dendrite. Bottom, [Cl-]i concentration at the end of the 1 s simulations as a function of distance from the soma. Both inhibitory synaptic input alone (blue trace) and excitatory input alone (red trace) caused selective increases in [Cl-]i in the distal dendrite. Balanced input (purple trace) caused an even greater increase in dendritic [Cl-]i. (B) Heatmap of neuronal firing rates as a function of different numbers of excitatory and inhibitory synapses used to select “balanced” synaptic configurations: i.e. pairs of excitatory-inhibitory (E:I) synapse numbers that could transform 5 Hz balanced input into 5 Hz output under conditions of dynamic Cl- (pale squares). (C) Heatmaps of [Cl-]i (shades of green) in the distal dendrite, proximal dendrite, soma, and axon at the end of the 1 s simulations when Cl- was allowed to evolve dynamically for three pairs of synaptic numbers reflecting “weak” inhibition (left, E:I– 200:30), “moderate” inhibition (E:I– 250:300) and “strong” inhibition (E:I– 300:800) at different balanced input frequencies. Spatial variations in [Cl-]i are dictated by the number of synapses and exaggerated by higher frequencies. (D) Top, schematic as in ‘A’ but with excitatory synapses targeted at the distal dendrite and the inhibitory synapses targeted at the proximal dendrite. Bottom, as in ‘A’, peri-somatic inhibitory synaptic input also produces spatial variations in [Cl-]i, but of smaller magnitude than when inhibitory synapses are distally located. (E) Heatmap as in ‘B’ but with proximal inhibition. This allowed E:I synapse pairs which produced 5 Hz output following 5 Hz input to be identified (pale squares). (F) While functionally similar to synapse pairs with distally targeted inhibition in ‘C’, pairs with proximal inhibition produced more modest changes in [Cl-]i as a function of the subcellular domain.