GABAergic control of dendritic calcium dynamics in striatal medium spiny neurons

Abstract

Event Abstract Back to Event GABAergic control of dendritic calcium dynamics in striatal medium spiny neurons Johannes Hjorth1*, Patrik Krieger2, Rodrigo F. Oliveira3, Kim T. Blackwell3 and Jeanette H. Kotaleski1 1 Royal Institute of Technology , Sweden 2 Karolinska Institute, Sweden 3 Krasnow Institute, United States Introduction: Experiments have demonstrated the ability of action potentials to actively backpropagate in striatal medium spiny (MS) neurons, affecting the calcium levels in the dendrites [1, 2, 3]. Increased calcium levels trigger changes in plasticity [4, 5], which is important for learning and other functions [6]. Studies in the hippocampus have shown that GABAergic input can modulate the backpropagation of action potentials from the soma to the distal dendrites [7]. The MS neurons receive both proximal feedforward GABAergic inhibition from fast spiking interneurons (FS), and distal feedback inhibition from other neighbouring MS neurons. In the present study the effect of GABAergic inputs on the dendritic calcium dynamics is investigated. Model: A previously published MS model [8] was reimplemented in GENESIS. The dendritic axial resistance and sodium conductances have been modified to better fit experimental results [1, 2, 3]. For example, in the modified model, backpropagation of dendritic action potentials requires sodium channel activation, and fails if those channels are blocked [1]. The MS neuron was activated by simulated AMPA/NMDA and GABAergic synaptic inputs [8], or by somatic current injections. Computational and experimental investigation: In this study we compare the effect of FS and MS synaptic inhibition on the backpropagation of action potentials in the MS model. Preliminary results suggest that GABAerigic inputs in distal dendrites can decrease the backpropagating action potential, and thus can reduce dendritic calcium levels, even though the cell is still spiking in the soma. These findings might suggest that feedback inhibition can control how prone the neighbouring MS neurons will be to plastic changes. These model predictions are further tested in experiments. The effect of GABAergic input on backpropagation of action potentials is investigated using two-photon calcium imaging from spines and dendrites on striatal neurons.