Integrins are cell adhesion heterodimers that mediate cell-cell and cell-extracellular matrix (ECM) interactions. They regulate various cellular functions in the central nervous system such as the localization of ion channels, calcium (Ca2+) homeostasis and synaptic transmission. Impairment of these functions can lead to neurodevelopment disorders such as Autism Spectrum Disorders (ASD). Small-conductance Ca2+-activated K+ channels (SK channels) are responsible for the medium afterhyperpolarization (mAHP) current (mIAHP) that regulates excitability and firing pattern in many neurons. I investigated firing properties of layer V pyramidal neurons of the medial prefrontal cortex (mPFC) in WT and Itgb3, the murine gene encoding the β3 integrin subunit, KO mice. I could distinguish two populations of pyramidal neurons in layer V (LV): extratelencephalic (ET) and intratelencephalic (IT). By using electrophysiological recordings and pharmacology, I identify a mIAHP in both types of neurons and in both genotypes, albeit with different characteristics: mIAHP is larger and faster in ET than in IT neurons; in the Itgb3 KO, the mIAHP is smaller in ET neurons, as compared to WT. Furthermore, the SK channel-specific blocker apamin affects differently the firing pattern of ET and IT neurons; it increases adaptation in ET neurons, while having no significant effect in IT neurons. To complement the electrophysiological results, I used viral retrograde labelling to investigate expression of β3 integrin and SK channel in both neuronal types. Altogether, my findings indicate that β3 integrin regulates the mIAHP and the firing properties of layer V pyramidal neurons, although to different degrees in ET and IT neurons. These differences might mirror the diverse genetic, anatomy and function of the two neuron subpopulations, allowing them to respond differently to external perturbations that can promote neurodevelopment disorders.

β3 integrin-dependent regulation of SK channel-mediated Ca2+-activated K+ currents in intra- and extra-telencephalic cortical pyramidal neurons

VITALE, CARMELA
2020-03-13

Abstract

Integrins are cell adhesion heterodimers that mediate cell-cell and cell-extracellular matrix (ECM) interactions. They regulate various cellular functions in the central nervous system such as the localization of ion channels, calcium (Ca2+) homeostasis and synaptic transmission. Impairment of these functions can lead to neurodevelopment disorders such as Autism Spectrum Disorders (ASD). Small-conductance Ca2+-activated K+ channels (SK channels) are responsible for the medium afterhyperpolarization (mAHP) current (mIAHP) that regulates excitability and firing pattern in many neurons. I investigated firing properties of layer V pyramidal neurons of the medial prefrontal cortex (mPFC) in WT and Itgb3, the murine gene encoding the β3 integrin subunit, KO mice. I could distinguish two populations of pyramidal neurons in layer V (LV): extratelencephalic (ET) and intratelencephalic (IT). By using electrophysiological recordings and pharmacology, I identify a mIAHP in both types of neurons and in both genotypes, albeit with different characteristics: mIAHP is larger and faster in ET than in IT neurons; in the Itgb3 KO, the mIAHP is smaller in ET neurons, as compared to WT. Furthermore, the SK channel-specific blocker apamin affects differently the firing pattern of ET and IT neurons; it increases adaptation in ET neurons, while having no significant effect in IT neurons. To complement the electrophysiological results, I used viral retrograde labelling to investigate expression of β3 integrin and SK channel in both neuronal types. Altogether, my findings indicate that β3 integrin regulates the mIAHP and the firing properties of layer V pyramidal neurons, although to different degrees in ET and IT neurons. These differences might mirror the diverse genetic, anatomy and function of the two neuron subpopulations, allowing them to respond differently to external perturbations that can promote neurodevelopment disorders.
13-mar-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/996218
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