Biology subjects

Rama, S.

Publications and source records attributed to Rama, S..

5 recordsLinked to original sources

bioRxiv2024

Na+/Ca2+ exchanger triggers transient disruption of axon initial segments in hippocampal granule cells after brief ischemia.

The axon initial segment (AIS) is the site of action potential initiation in many cell types. The large density of Na+ channels and the small intraluminal volume of the AIS underlie the largest spike-dependent Na+ raise along the neuron. Our Na+ and Ca2+ imaging experiments in dentate granule cells reveal that the Na+/Ca2+ exchanger contributes to fast Na+ clearance at the expense of Ca2+ entry specifically at the AIS during short bursts of action potentials. The AIS is thought to be irreversibly disrupted during brain ischemia by the Ca2+-dependent protease calpain, as an early step leading to neuronal death. We find here that brief transitory ischemia produces a similar calpain-dependent disruption of the AIS in the dentate gyrus. However, this is not an irreversible process: a few days following the brief ischemic stress, intact initial segments re-appear, and calpain activity in the dentate gyrus returns to normal. Moreover, pharmacological blockade of Ca2+ entry through the Na+/Ca2+ exchanger prevents AIS disruption in vivo and in slice preparations. Our results unveil a highly dynamic anoxia driven disruption-reconstruction of AIS, which is mediated by a previously unnoticed Ca2+ entry through the Na+/Ca2+ exchanger in the axon initial segment of hippocampal granule cells.

neuroscience↗

bioRxiv2022

Pliable synaptic fidelity and excitatory inter-synaptic crosstalk in the intact brain

Memory formation in neural circuits may involve changes in synaptic efficacy and in cell intrinsic excitability, yet how this process unfolds in the living brain has remained elusive. Here, we employed multiplexed imaging of genetically encoded indicators of glutamate and Ca2+ in mouse barrel cortex to detect increased fidelity coupled with reduced excitation of thalamocortical connections that undergo whisker-stimulation induced LTP. High-resolution imaging revealed that whisker stimuli trigger excitatory synaptic activity that generates extrasynaptic glutamate transients reaching the bulk of neighbouring synapses in the target cortical area. Our findings pave the way to understanding basic plasticity features of the synaptic connectome while revealing a significant component of volume-transmitted glutamatergic signalling among cells in the intact brain. One Sentence SummarySensory-stimulation LTP increases fidelity while reducing excitation at individual thalamocortical connections which generate spatially intersecting glutamate discharges

neuroscience↗

bioRxiv2021

Homeostatic regulation of axonal Kv1.1 channels accounts for both synaptic and intrinsic modifications in CA3 circuit

Homeostatic plasticity of intrinsic excitability goes hand-in-hand with homeostatic plasticity of synaptic transmission. However, the mechanisms linking the two forms of homeostatic regulation have not been identified so far. Using electrophysiological, imaging and immunohistochemical techniques, we show here that blockade of excitatory synaptic receptors for 2-3 days induces an up-regulation of synaptic strength at CA3-CA3 connexions and intrinsic excitability of CA3 pyramidal neurons. Activity-deprived connexions were found to express a high release probability, an insensitivity to dendrotoxin, and a lack of depolarization-induced presynaptic facilitation, indicating a loss of presynaptic Kv1.1 function. The down-regulation of Kv1.1 channels in activity-deprived neurons was confirmed by their broader action potentials measured in the axon that were insensitive to dendrotoxin. We conclude that regulation of axonal Kv1.1 channel constitutes a unique mechanism linking intrinsic excitability and synaptic strength that accounts for the functional synergy existing between homeostatic regulation of intrinsic excitability and synaptic transmission.

neuroscience↗

bioRxiv2020

A quick and easy way to estimate entropy and mutual information for neuroscience

AO_SCPLOWBSTRACTC_SCPLOWCalculations of entropy of a signal or mutual information between two variables are valuable analytical tools in the field of neuroscience. They can be applied to all types of data, capture nonlinear interactions and are model independent. Yet the limited size and number of recordings one can collect in a series of experiments makes their calculation highly prone to sampling bias. Mathematical methods to overcome this so-called "sampling disaster" exist, but require significant expertise, great time and computational costs. As such, there is a need for a simple, unbiased and computationally efficient tool for estimating the level of entropy and mutual information. In this paper, we propose that application of entropy-encoding compression algorithms widely used in text and image compression fulfill these requirements. By simply saving the signal in PNG picture format and measuring the size of the file on the hard drive, we can estimate entropy changes through different conditions. Furthermore, with some simple modifications of the PNG file, we can also estimate the evolution of mutual information between a stimulus and the observed responses through different conditions. We first demonstrate the applicability of this method using white-noise-like signals. Then, while this method can be used in all kind of experimental conditions, we provide examples of its application in patch-clamp recordings, detection of place cells and histological data. Although this method does not give an absolute value of entropy or mutual information, it is mathematically correct, and its simplicity and broad use make it a powerful tool for their estimation through experiments.

neuroscience↗

bioRxiv2019

Axonal Na+ channels detect and transmit levels of input synchrony in local brain circuits

Sensory processing requires mechanisms of fast coincidence-detection to discriminate synchronous from asynchronous inputs. Spike-threshold adaptation enables such a discrimination but is ineffective in transmitting this information to the network. We show here that presynaptic axonal sodium channels read and transmit precise levels of input synchrony to the postsynaptic cell by modulating the presynaptic action potential (AP) amplitude. As a consequence, synaptic transmission is facilitated at cortical synapses when the presynaptic spike is produced by synchronous inputs. Using dual soma-axon recordings, imaging, and modeling, we show that this facilitation results from enhanced AP amplitude in the axon due to minimized inactivation of axonal sodium-channels. Quantifying local circuit activity and using network modeling, we found that spikes induced by synchronous inputs produced a larger effect on network activity than spikes induced by asynchronous inputs. Therefore, this input-synchrony dependent facilitation (ISF) may constitute a powerful mechanism regulating spike transmission.

neuroscience↗