Neuronal gain modulability is determined by dendritic morphology: A computational optogenetic study

Abstract

The mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable. To investigate how different topologies of the neuronal dendritic tree affect the neuron’s input-output characteristics we generate branching geometries which replicate morphological features of most common neurons, but keep the number of branches and overall area of dendrites approximately constant. We found a relationship between a neuron’s gain modulability and its dendritic morphology, with neurons with bipolar dendrites with a moderate degree of branching being most receptive to control of the gain of their input-output relationship. The theory was then tested and confirmed on two examples of realistic neurons: 1) layer V pyramidal cells—confirming their role in neural circuits as a regulator of the gain in the circuit in addition to acting as the primary excitatory neurons, and 2) stellate cells. In addition to providing testable predictions and a novel application of dual-opsins, our model suggests that innervation of all dendritic subdomains is required for full gain modulation, revealing the importance of dendritic targeting in the generation of neuronal gain control and the functions that it subserves. Finally, our study also demonstrates that neurophysiological investigations which use direct current injection into the soma and bypass the dendrites may miss some important neuronal functions, such as gain modulation.

Optogenetic stimulation of the VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the auditory cortex

“…This enhancement of infragranular activity was locally relayed to supragranular layers I/II. This mechanism may provide a way for intratelencephalic neurons in infragranular layers 44 to provide a translaminar gain control of sensory representation depending on the experience of reward 45,46 . Although direct projections of the ipsilateral VTA provide a significant contribution to non-sensory inputs of the gerbil ACx 6 , our approach may recruit other relay stations that could contribute to the observed effects 5 .…”

Modulation of the dynamics of cerebellar Purkinje cells through the interaction of excitatory and inhibitory feedforward pathways

“…The stimulus-response, or input-output, relationship of single neurons is a fundamental feature for neural dynamics. A change in the gradient input-output function of a neuron, termed gain modulation, is associated with several factors, including shunting inhibition, synaptic noise, and dendritic morphology [50][51][52][53]. Here, we investigated the contribution of synaptic input to gain modulation taking into account the effect of MLI inhibition and STP of excitation, which can modulate PC discharges in response to GC inputs.…”

NeuroMorphoVis: a collaborative framework for analysis and visualization of neuronal morphology skeletons reconstructed from microscopy stacks

“…Volumetric models of neuronal tissue are crucial for performing specific neuroscientific analysis studies ( Favre-Bulle et al , 2015 ; Jarvis et al , 2017 ; Nikolic et al , 2013 ) and in silico experiments ( Abdellah et al , 2015 , 2017a ; Markram et al , 2015 ). They can be also exploited for comparative morphometric studies for validating reconstructed morphologies in volumetric form from microscopy stacks with respect to the ones extracted from vector-based representation.…”