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Title: Dendritic integration of synaptic inputs in the stellate cells of the medial entorhinal cortex
Author: Toleikyte, G.
ISNI:       0000 0004 5367 2732
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Grid cells fire action potentials at regular intervals in space, giving rise to a spectacularly regular and stable hexagonal arrangement of firing fields (Hafting et al., 2005). For this reason they have been proposed to represent a neural code for path integration (McNaughton et al., 2006). Grid cells have primarily been found in layer II of the medial entorhinal cortex (MEC) (Hafting et al., 2005). In this thesis I explore the dendritic properties of putative grid cells in MEC layer II and how they may contribute to generating the grid cell firing pattern. To assess the spatial and temporal dynamics of dendritic integration I have used patterned two-photon glutamate uncaging in vitro in combination with somatic whole cell recordings. My findings suggest that the principal neurons of MEC are highly excitable, exhibiting supralinear summation of near-simultaneous inputs and fast and slow dendritic spikes. Supralinear summation is timing-dependent and inputs are summated in a linear manner if separated by 8 ms time intervals. In order to understand the biophysical mechanisms of supralinear summation I blocked NMDA receptors and voltage-gated sodium channels (VGSCs) with D-AP5 and TTX respectively. Both supralinearity and dendritic spikes were abolished in the presence of both blockers, while TTX alone reduced supralinearity and abolished fast but not slow dendritic spikes. This suggests that fast dendritic spikes are largely mediated by VGSCs and slow dendritic spikes by NMDA receptors. Furthermore, I have assessed dendritic integration in physiologically relevant conditions by injecting current waveform to produce in vivo-like membrane potential dynamics, recorded when an animal was crossing a firing field of a MEC II principal neuron in a virtual environment (Schmidt-Hieber & Häusser, 2013). In vivo-like membrane potential dynamics increased supralinearity of the integral of EPSPs and probability of dendritic spikes. These findings have been integrated in a continuous attractor network model of grid cell firing by Christoph Schmidt-Hieber, to assess their relevance for the grid cell rate and temporal code, that revealed that supralinear dendritic integration increases grid cell rate code robustness and fast dendritic sodium spikes increase the precision of the temporal code (phase precession) of grid cells. To conclude, in this thesis I demonstrated that dendrites of principal neurons of MEC layer II integrate synaptic inputs in a highly supralinear manner, mediated by the VGSCs and NMDARs and boosted by putative dendritic spikes. Both supralinearity and proportion of dendritic spikes are increased under in vivo-like membrane potential dynamics. These findings suggest the hypothesis for the intracellular mechanisms that mediate the robustness of grid cell firing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available