Inhibitory Synaptic Plasticity and Gain Modulation in Cerebellar Nucleus Neurons

Neurons can encode information using the rate of their action potentials, making the relation between input rate and output rate a prominent feature of neuronal information processing. This relation, known as I-O function, can rapidly change in response to various factors or neuronal processes. Most noticeably, a neuron can undergo a multiplicative operation, resulting in a change of the slope of its I-O curve, also know as gain change. Gain changes represent multiplicative operations, and they are wide- spread. They have been found to play an important role in the encoding of spatial location and coordinate transformation, to signal amplification, and other neuronal functions. One of the factors found to introduce and control neuronal gain is synaptic Short Term Depression (STD). We use both integrate-and- re and conductance based neuron models to identify the effect of STD in excitatory and inhibitory modulatory input. More specifically, we are interested in the effect of STD at the inhibitory synapse from Purkinje cells to cerebellar nucleus neurons. Using a previously published, biologically realistic model, we find that the presence of STD results in a gain change. Most importantly we identify STD at the inhibitory synapse to enable excitation-mediated gain control. To isolate the mechanism that allows excitation to control gain, even though STD is applied at a different synapse, we first show that the overall effect is mediated by average conductance. Having done this, we find that the effect of STD is based on the non-linearity introduced in the relation between input rate and average conductance. We find this effect to vary, depending on the position of the I-O function on the input rate axis. Modulatory input shifts the I-O curve along the input rate axis, consequently shifting it to a position where STD has a different effect. The gain differences in the STD effects between the two positions enable excitation to perform gain control

Determinants of gain modulation enabled by short-term depression at an inhibitory cerebellar synapse

Abstract from the 23rd Annual Computational Neuroscience Meeting: CNS 2014. © 2014 Bampasakis et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedNeurons adapt rapidly the slope, also known as gain, of their input-output function to time-varying conditions. Gain modulation is a prominent mechanism in many brain processes, such as auditory processing and attention scaling of orientation tuning curves.Peer reviewe

Interoperability in the GENESIS 3.0 Software Federation : the NEURON Simulator as an Example

© 2013 Cornelis et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Poster presented at CNS 2013Non peer reviewe

Short-term depression of inhibitory Purkinje cell synapses enhances gain modulation in the cerebellar nuclei

© 2013 Bampasakis et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Poster presented at CNS 2013Peer reviewe

Multiplicative gain modulation arising from inhibitory synaptic plasticity in the cerebellar nuclei

4th NAMASEN Training Workshop - Dendrites 2014Neurons use the rate of action potentials to encode sensory variables. This makes the output rate as a function of input, also known as input-output (I–O) relationship, a core computational function in neuronal processing. The introduction, or increase, of a modulatory input, can transform this function in multiple ways: additive transformations result in a shift, and multiplicative transformations in a change of slope of the I–O relationship. This slope change is known as gain modulation, and it can implement important forms of neural computation such as coordinate transformations. Gain modulation can be found in a wide range of brain systems, including the cerebellum, where it can be enabled by synaptic plasticity at both excitatory and inhibitory synapses. We use a realistic, conductance based, multi-compartmental model of a cerebellar nucleus (CN) neuron, to investigate the determinants of gain modulation mediated by synaptic plasticity. In particular, we are interested in the effect of short term depression (STD) at the inhibitory synapse from Purkinje cells (PCs) to CN neurons. Considering the inhibitory PC input as the driving input, we compare the I–O relationship of the CN neuron in the presence and absence of STD for 20 Hz of excitatory synaptic input from mossy fibers (MFs), and find that STD introduces a gain change, changing the slope of the I–O function. We then proceed to compare the transformation performed by the increase of the modulatory input from 20 to 50 Hz, in the presence and absence of STD. We find that the presence of STD in the inhibitory synapse introduces a multiplicative component in the transformation performed by the excitatory input, an effect that persists for different levels of STD, and various combinations of regularity and synchronicity in the input.Peer reviewe