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After last month’s successful launch , it is finally time for the April edition of MaxWell Monthly Must-Reads. This month’s blog series will focus on Neuronal Excitability. The topic plays a key role in understanding how neurons encode and transmit information. At MaxWell Biosystems, we aim to develop assays for characterizing neuronal excitability, both in healthy and disease conditions. For this month’s MMM, we include recent studies on different factors that regulate excitability of neurons, such as ion channels, calcium signaling, and axons.
- PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity
by Floriana Fruscione, Pierluigi Valente, Bruno Sterlini, Alessandra Romei, Simona Baldassari, Manuela Fadda, Cosimo Prestigio, Giorgia Giansante, Jacopo Sartorelli, Pia Rossi, Alicia Rubio, Antonio Gambardella, Thierry Nieus, Vania Broccoli, Anna Fassio, Pietro Baldelli, Anna Corradi, Federico Zara & Fabio Benfenati. Brain. April 2018.
This study explores the role of proline-rich transmembrane protein 2 (PRRT2) in modulating Na+ channels of neurons. The authors used electrophysiology and imaging to determine phenotypes related to PRRT2. Results showed that the lack of PRRT2 induced hyperactivity of voltage-dependent Na+ channels. Read the paper here. - Aberrant calcium signaling in astrocytes inhibits neuronal excitability in a human Down syndrome stem cell model
by Lin Tian, Grace Or, Yinxue Wang, Guilai Shi, Yizhi Wang, Junqing Sun, Stelios Papadopoulos, Gerard Broussard, Elizabeth Unger, Wenbin Deng, Jason Weick, Anita Bhattacharyya, Chao-Yin Chen, Guoqiang Yu & Loren Looger. Preprint in bioRxiv. January 2018.
This paper aims to study astrocyte interactions associated with neurological disorders. The authors developed an in vitro cell culture system combining neurons and astrocytes differentiated from Down syndrome (DS) patient-derived induced pluripotent stem cells (iPSCs). DS Astroglia were shown to have increased frequency of spontaneous calcium fluctuations that reduced the excitability of co-cultured neurons. Read the paper here. - Signal propagation along the axon
by Sylvain Rama, Mickaël Zbili & Dominique Debanne. Current Opinion in Neurobiology. August 2018.
This review highlights the mechanisms involved in the propagation of action potentials along axons. The axon’s characteristics influence reliable transmission of information in the brain. Key concepts in this review include the compartmentalization of action potential waveform in different axonal segments and the effect of axon morphology on conduction velocity. Read the paper here. - All for one but not one for all: Excitatory synaptic scaling and intrinsic excitability are coregulated by CaMKIV, whereas inhibitory synaptic scaling is under independent control
by Annelise Joseph and Gina G. Turrigiano. Journal of Neuroscience. July 2017.
This paper investigates how Calcium/calmodulin-dependent protein kinase type IV (CaMKIV) regulates excitability and synaptic scaling in neocortical circuits. The authors manipulated CaMKIV signaling in individual neurons and measured homeostatic plasticity in the form of synaptic excitation, synaptic inhibition, and intrinsic excitability. Read the paper here. - Axogenic mechanism enhances retinal ganglion cell excitability during early progression in glaucoma
by Michael L. Risner, Silvia Pasini, Melissa L. Cooper, Wendi S. Lambert & David J. Calkins. PNAS. March 2018.
This work studied neurodegeneration through experimental glaucoma, wherein individual retinal ganglion cells (RGCs) were analyzed while applying increased pressure (short-term) on the retina. The authors found dendritic pruning by week 2 of pressure elevation, however, light response of RGCs was not lost. Instead, RGCs demonstrated a transient increase in axon firing response to the preferred light stimulus due to increase of voltage-sensitive sodium channels in the axon. Read the paper here. More information can be found here and here.