Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing

T-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

Modeling the effect of temperature on membrane response of light stimulation in optogenetically-targeted neurons

Optogenetics is revolutionizing neuroscience but an often neglected effect of light stimulation of the brain is the generation of heat. In extreme cases, light-generated heat kills neurons but mild temperature changes alter neuronal function. In this work, we investigated heat transfer in brain tissue for common optogenetic protocols using the finite element method. We then modeled channelrhodopsin-2 in a single- and a spontaneous-firing neuron to explore the effect of heat in light stimulated neurons. We found that, at commonly used intensities, laser radiation considerably increases the temperature in the surrounding tissue. This effect alters action potential size and shape and cause increase in spontaneous firing frequency in a neuron model. However, the shortening of activation time constants generated by heat in the single firing neuron model produce AP failures in response to light stimulation. We also found changes in the power spectrum density and a reduction in the time required for synchronization in an interneuron network model of gamma oscillations. Our findings indicate that light stimulation with intensities used in optogenetic experiments may affect neuronal function not only by direct excitation of light sensitive ion channels and/or pumps but also by generating heat. This approach serves as a guide to design optogenetic experiments that minimize the role of tissue heating in the experimental outcome.

Modeling the effect of temperature on membrane response of light stimulation in optogenetically-targeted neurons

Optogenetics is revolutionizing neuroscience but an often neglected effect of light stimulation of the brain is the generation of heat. In extreme cases, light-generated heat kills neurons but mild temperature changes alter neuronal function. In this work, we investigated heat transfer in brain tissue for common optogenetic protocols using the finite element method. We then modeled channelrhodopsin-2 in a single- and a spontaneous-firing neuron to explore the effect of heat in light stimulated neurons. We found that, at commonly used intensities, laser radiation considerably increases the temperature in the surrounding tissue. This effect alters action potential size and shape and cause increase in spontaneous firing frequency in a neuron model. However, the shortening of activation time constants generated by heat in the single firing neuron model produce AP failures in response to light stimulation. We also found changes in the power spectrum density and a reduction in the time required for synchronization in an interneuron network model of gamma oscillations. Our findings indicate that light stimulation with intensities used in optogenetic experiments may affect neuronal function not only by direct excitation of light sensitive ion channels and/or pumps but also by generating heat. This approach serves as a guide to design optogenetic experiments that minimize the role of tissue heating in the experimental outcome.

Synchronization Dynamics of Two Heterogeneous Chaotic Rulkov Neurons with Electrical Synapses

Two heterogeneous chaotic Rulkov neurons with electrical synapses are investigated in this paper. First, we study the ability of the second neuron to modify the dynamics of the first neuron. It is shown that when the parameters of the first neuron are located at the vicinity of the Neimark–Sacker bifurcation curves the first firing neuron can be controlled into the quiescent state when coupled with the second neuron. While the parameters of the first neuron are near the flip bifurcation curves the first firing neuron cannot be suppressed. Second, we discuss burst synchronization for two bursting neurons and two tonic spiking neurons. It is shown that two heterogeneous chaotic Rulkov neurons with tonic spiking firing cannot reach anti-phase synchronization under the inhibitory coupling, which is different from the property of nonchaotic Rulkov neurons. Finally, we show that for two bursting neurons if the coupling is strong enough then burst synchronization can be converted into spike synchronization. However, complete synchronization cannot be achieved for any strong coupling.

PRESYNAPTIC LEARNING AND MEMORY WITH A PERSISTENT FIRING NEURON AND A HABITUATING SYNAPSE: A MODEL OF SHORT TERM PERSISTENT HABITUATION

Our paper explores the interaction of persistent firing axonal and presynaptic processes in the generation of short term memory for habituation. We first propose a model of a sensory neuron whose axon is able to switch between passive conduction and persistent firing states, thereby triggering short term retention to the stimulus. Then we propose a model of a habituating synapse and explore all nine of the behavioral characteristics of short term habituation in a two neuron circuit. We couple the persistent firing neuron to the habituation synapse and investigate the behavior of short term retention of habituating response. Simulations show that, depending on the amount of synaptic resources, persistent firing either results in continued habituation or maintains the response, both leading to longer recovery times. The effectiveness of the model as an element in a bio-inspired memory system is discussed.