Nikolic, K. | bioRxiv Science

bioRxiv2017

Platform for Closed Loop Neuromodulation Based on Dual Mode Biosignals

Closed loop neuromodulation, where the stimulation is controlled autonomously based on physiological events, has been more effective than open loop techniques. In the few existing closed loop implementations which have a feedback, indirect non-neurophysiological biomarkers have been typically used (e.g. heart rate, stomach distension). Although these biomarkers enable automatic initiation of neural stimulation, they do not enable intelligent control of stimulation dosage. In this paper, we present a novel closed loop neuromodulation platform based on a dual signal mode that is detecting electrical and chemical signatures of neural activity. We demonstrated it on a case of vagus nerve stimulation (VNS). Vagal chemical (pH) signal is detected and used for initiatisng VNS and vagal compound action potential (CAP) signals are used to determine the stimulation dosage and pattern. Although we used the paradigm of appetite control and neurometabolic therapies, the platform developed here can be utilised for prototyping closed loop neuromodulation systems before adapting the final System-on-Chip (SoC) design.

bioengineering↗

bioRxiv2016

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

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 neurons 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 neurons 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.\n\nAuthor SummaryO_LIGain modulability indicated by dendritic morphology\nC_LIO_LIPyramidal cell-like shapes optimally receptive to modulation\nC_LIO_LIAll dendritic subdomains required for gain modulation, partial illumination is insufficient\nC_LIO_LIComputational optogenetic models improve and refine experimental protocols\nC_LI

neuroscience↗