Abstract
Cyclin-dependent kinase 5 (Cdk5) has been shown to play a critical role in brain development, learning, memory and neural processing in general. Cdk5 is widely distributed in many neuron types in the central nervous system, while its cell-specific role is largely unknown. Our previous study showed that Cdk5 inhibition restored ocular dominance (OD) plasticity in adulthood. In this study, we specifically knocked down Cdk5 in different types of neurons in the visual cortex and examined OD plasticity by optical imaging of intrinsic signals. Downregulation of Cdk5 in parvalbumin-expressing (PV) inhibitory neurons, but not other neurons, reactivated adult mouse visual cortical plasticity. Cdk5 knockdown in PV neurons reduced the evoked firing rate, which was accompanied by an increment in the threshold current for the generation of a single action potential (AP) and hyperpolarization of the resting membrane potential. Moreover, chemogenetic activation of PV neurons in the visual cortex can attenuate the restoration of OD plasticity by Cdk5 inhibition. Taken together, our results suggest that Cdk5 in PV interneurons may play a role in modulating the excitation and inhibition balance to control the plasticity of the visual cortex.
Highlights
Academic Editor: Elek MolnárCyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase expressed abundantly in post-mitotic neurons and plays a vital role in different brain regions [1,2]
Using optical imaging of intrinsic signals in V1, we found that downregulation of Cdk5 activity in PV neurons, but not other cell types, facilitated a remarkable restoration of ocular dominance (OD) plasticity in adults, which was mediated by the downregulation of the inhibitory activity of PV neurons
Cdk5 is widely distributed in various tissues, but its kinase activity is restricted in neurons [27,28]
Summary
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase expressed abundantly in post-mitotic neurons and plays a vital role in different brain regions [1,2]. It has been reported that overactivity of Cdk is associated with neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease and Huntington’s disease [2,3,4]. Hyperactive Cdk in the striatum results in loss of cocaine sensitization and motor coordination deficits [5]. Pharmacological inhibition of Cdk in the nucleus accumbens enhances the locomotor-activating and incentive-motivational effects of cocaine [6]. The role of Cdk in the visual cortex is largely unknown. Downregulation of Cdk activity by pharmacological inhibition or genetic knockdown rejuvenates the visual cortex and enhances the synaptic plasticity of the adult mouse visual cortex [9], but the underlying mechanism remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
