Functional study of interneuron properties within first and higher order thalamic regions
File(s)
Author(s)
Djama, Deyl Said
Type
Thesis
Abstract
The thalamus serves as a relay station for sensory information (except smell) and plays a critical role in regulating arousal, motor control, pain, and memory. While its broad connectivity is well-documented, the role of local interneurons in the thalamus is less understood. This study investigates how thalamic interneurons, particularly Sox14-expressing (Sox14-INs) and Parvalbumin-expressing (PV-INs) interneurons, modulate information processing through GABA-A receptor-mediated inhibition.
The thesis first explores the impact of GABA release from local interneurons onto thalamocortical (TC) neurons in three sensory thalamic regions: the dorsal lateral geniculate (LGd) nucleus, the lateral posterior (LP) nucleus, and the ventrobasal (VB) complex. Sox14-IN density was highest in LGd and lowest in VB. Whole-cell voltage-clamp recordings showed that the LP region exhibited the lowest rate of inhibitory postsynaptic currents (IPSCs), while slow IPSC kinetics associated with dendrodendritic neurotransmitter release in Sox14-INs were prominent in LGd and LP but sparse in VB. Fast IPSCs, associated with conventional phasic GABA release, were observed in all regions. Sox14-IN firing also increased tonic conductance onto TC neurons through extra-synaptic GABA-A receptor activation.
Next, I developed dynamic-clamp protocols to mimic retinal ganglion cell (RGC) firing patterns at the retinogeniculate synapse, in addition to the fast, slow, and tonic forms of inhibition released by local interneurons. In the absence of inhibition, TCs transmitted information from OFF-type RGCs more effectively than ON-type cells. Slow and tonic inhibitions shifted input selectivity to lower frequencies, while tonic inhibition improved information transfer across all RGC input patterns.
Finally, I compared Sox14-INs with PV-INs in first and higher order thalamic nuclei. While both types had similar morphologies, PV-INs exhibited clear distinct biophysical properties compared to Sox14-INs. Paired recordings of Sox14-INs demonstrated clear inter-connectivity, however, future work will be needed to determine if this is also a feature of PV-INs.
The thesis first explores the impact of GABA release from local interneurons onto thalamocortical (TC) neurons in three sensory thalamic regions: the dorsal lateral geniculate (LGd) nucleus, the lateral posterior (LP) nucleus, and the ventrobasal (VB) complex. Sox14-IN density was highest in LGd and lowest in VB. Whole-cell voltage-clamp recordings showed that the LP region exhibited the lowest rate of inhibitory postsynaptic currents (IPSCs), while slow IPSC kinetics associated with dendrodendritic neurotransmitter release in Sox14-INs were prominent in LGd and LP but sparse in VB. Fast IPSCs, associated with conventional phasic GABA release, were observed in all regions. Sox14-IN firing also increased tonic conductance onto TC neurons through extra-synaptic GABA-A receptor activation.
Next, I developed dynamic-clamp protocols to mimic retinal ganglion cell (RGC) firing patterns at the retinogeniculate synapse, in addition to the fast, slow, and tonic forms of inhibition released by local interneurons. In the absence of inhibition, TCs transmitted information from OFF-type RGCs more effectively than ON-type cells. Slow and tonic inhibitions shifted input selectivity to lower frequencies, while tonic inhibition improved information transfer across all RGC input patterns.
Finally, I compared Sox14-INs with PV-INs in first and higher order thalamic nuclei. While both types had similar morphologies, PV-INs exhibited clear distinct biophysical properties compared to Sox14-INs. Paired recordings of Sox14-INs demonstrated clear inter-connectivity, however, future work will be needed to determine if this is also a feature of PV-INs.
Version
Open Access
Date Issued
2024-08-01
Date Awarded
01/12/2024
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Brickley, Stephen G
Isalan, Mark
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)