Dendritic properties of inhibitory thalamic neurons: implications in sub-cortical sensory processing

dorsal lateral geniculate nucleus;thalamic reticular nucleus;T-type calcium channels;presynaptic dendrite;local inhibition;whole cell recording;glutamate uncaging;two photon imaging;dendrite;glutamate receptor;feedforward inhibition;thalamus;interneuron

Crandall, Shane

关键词: dorsal lateral geniculate nucleus;    thalamic reticular nucleus;    T-type calcium channels;    presynaptic dendrite;    local inhibition;    whole cell recording;    glutamate uncaging;    two photon imaging;    dendrite;    glutamate receptor;    feedforward inhibition;    thalamus;    interneuron;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/31947/Crandall_Shane.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

This dissertation is focused on understanding the cellular mechanisms underlying thalamocortical network activities. Specifically, I am interested in how inhibitory neurons of the thalamus process information received from other neurons before passing it along to other network targets. Like many neurons in the central nervous system, inhibitory neurons of the thalamus receive thousands of synaptic inputs from other neurons, most of which contact their treelike extensions called dendrites. When these inputs are activated they create electrical signals that travel across the dendrites. If the signals are strong enough, the neuron will generate action potentials, thereby communicating the information to other neurons. The process of turning input into output is often referred to as “synaptic integration” and is a fundamental process performed by all neurons. I believe understanding how information integration occurs within the dendrites of inhibitory thalamic neurons, as it relates to their organization within the network, will provide valuable insight as to the function of inhibition during thalamocortical activities. The importance of this work lies in the fact that brain processes such as sensory perception, behavioral arousal, attention, and certain pathophysiological conditions such as epilepsy result from the coordinated activities of inhibitory and excitatory neurons in the thalamocortical circuit. In Chapter 1, I provide the reader with a comprehensive review of the research literature examining inhibitory thalamic neurons. The information presented in this chapter provides a detailed background of my completed studies (Chapter 2, 3, and 4). My initial study (Chapter 2) demonstrates that in thalamic reticular neurons, voltage-gated T-type calcium channels, located in distal dendrites, function to amplify excitatory afferent inputs. This powerful dendritic property ensures integration of distal input at the somatic level by compensating for any attenuation that would otherwise normally occur due to passive membrane properties. Given the unique voltage-sensitivity of the T-type calcium channel, our data suggests that the degree in which synaptic input would be “boosted” would strictly depends on the voltage-state of the somatodendritic axis. Moreover, if we consider the unique structural organization of the thalamic reticular nucleus, we hypothesize that such dendritic properties could facilitate intra- and cross-modal sensory integration at the level of the thalamus. This study is published in the Journal of Neuroscience. In my second study (Chapter 3), I show that the presynaptic dendrites of thalamic interneurons operate as independent input-output devices. This unique property allows the dendrites of thalamic interneurons to tightly regulate fast monosynaptic excitation in thalamocortical relay neurons. Given dendritic terminals operate independently of the axon and presumably each other, these results suggest that thalamic interneurons can function as multiplexing integrators. This study is published in the Journal of Neuroscience.In my last study (Chapter 4), I reveal that the dendrites of thalamic interneurons form two types of dendrodendritic synapses in the visual thalamus. These inhibitory dendrodendritic synapses targeted the same postsynaptic neurons and are either mediated by ionotropic or a combination of ionotropic and metabotropic glutamate receptors. Two types of dendrodendritic synapses suggest that retinogeniculate input can drive different inhibitory activity in the same relay neuron, through two distinct feedforward inhibitory pathways. Inhibitory output from these two terminals would likely shape how thalamocortical relay neurons respond to visual stimuli and communicate information to the neocortex.