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Title: The role of Cav3.2 Ca2+ channels in influencing the activity of the layer II stellate cells of the Medial Entorhinal Cortex
Author: Topczewska, Aleksandra Paulina
ISNI:       0000 0004 7229 7923
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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Layer II (L II) Medial Entorhinal Cortex (MEC) stellate cell (SC) intrinsic membrane properties vary along the MEC dorsal-ventral axis. This has been attributed partly to altered HCN and K+ conductances (Garden et al. 2008; Giocomo and Hasselmo 2008). The subthreshold active T-type CaV3.2 Ca2+ channels, though, are also expressed in the MEC (Huang et al. 2011). CaV3.2 channels are known to influence neuronal excitability but their effects on dorsal and ventral LII MEC SC properties remain unknown. To investigate this, I obtained acute brain slices from CaV3.2 wild type (CaV3.2+/+) and null (CaV3.2-/-) 5-8 week old mice and made electrophysiological recordings from dorsal and ventral L II MEC SC. CaV3.2-/- ventral neurons displayed significantly reduced input resistance but little difference in resting membrane potential (RMP) compared with CaV3.2+/+ ventral neurons. Consequently, depolarizing steps resulted in fewer action potentials in CaV3.2-/- ventral SC than in wild type neurons. In contrast, dorsal CaV3.2-/- and CaV3.2+/+ SC properties were similar. Furthermore, CaV3.2+/+ ventral cells had a significantly higher α excitatory post synaptic potentials (αEPSP) summation ratio (at 50 Hz) in comparison to CaV3.2-/- ventral neurons. The Cav3 inhibitors, NiCl2 and TTA-P2, also significantly reduced input resistance and action potential firing in CaV3.2+/+ ventral neurons, whilst having little effect on CaV3.2+/+ dorsal or CaV3.2-/- neurons. Furthermore, voltage-clamp experiments revealed a significantly greater T-type Cav3.2 Ca2+ current in ventral than dorsal neurons. Our results suggest that Cav3.2 channels selectively affect L II MEC ventral SC properties, thereby contributing to the intrinsic membrane gradient across the MEC dorsal-ventral axis.
Supervisor: Shah, M. M. ; Dolphin, A. C. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available