TRP Channels and Neural Persistent Activity

Abstract

One of the integrative properties of the nervous system is its capability to, by transient motor commands or brief sensory stimuli, evoke persistent neuronal changes, mainly as a sustained, tonic action potential firing. This neural activity, named persistent activity, is found in a good number of brain regions and is thought to be a neural substrate for short-term storage and accumulation of sensory or motor information [1]. Examples of this persistent neural activity have been reported in prefrontal [2] and entorhinal [3] cortices, as part of the neural mechanisms involved in short-term working memory [4]. Interestingly, the general organization of the motor systems assumes the presence of bursts of short-lasting motor commands encoding movement characteristics such as velocity, duration, and amplitude, followed by a maintained tonic firing encoding the position at which the moving appendage should be maintained [5, 6]. Generation of qualitatively similar sustained discharges have also been found in spinal and supraspinal regions in relation to pain processing [7, 8]. Thus, persistent neural activity seems to be necessary for both behavioral (positions of fixation) and cognitive (working memory) processes. Persistent firing mechanisms have been proposed to involve the participation of a non-specific cationic current (CAN current) mainly mediated by activation of TRPC channels. Because the function and generation of persistent activity is still poorly understood, here we aimed to review and discuss the putative role of TRP-like channels on its generation and/or maintenance.

The NCA sodium leak channel is required for persistent motor circuit activity that sustains locomotion

“…Pharmacological activation of some metabotropic cholinergic receptors, which activates CAN currents, induces persistent neural activity in the prefrontal cortex 21 , the hippocampus 22 , the entorhinal cortex 23 and the lateral amygdala 24 . Canonical transient receptor potential channels (TRPCs) have been proposed to underlie some CAN currents [25][26][27] . The lamprey reticulospinal neurons sustain action potential firing after a brief tap on the snout, which induces an escape response; the sustained neural activity requires CAN currents activated by the NMDA receptors 15,28 .…”

Mechanisms of Persistent Activity in Cortical Circuits: Possible Neural Substrates for Working Memory

“…Although the molecular identity of the ion channel mediating this response is unknown, it appears to be gated by Ca 2+ (or Ca 2+ ions bound to an accessory protein), is permeable to Na + and Ca 2+ , and is sensitive to flufenamic acid (FFA; Haj-Dahmane & Andrade 1999, Lei et al 2014, Rahman & Berger 2011, Tahvildari et al 2008, Zhang et al 2011), a nonsteroidal anti-inflammatory agent. Several groups have hypothesized that a subtype of transient receptor potential (TRP) channels may mediate I CAN responses, based on pharmacological studies (Lei et al 2014, Reboreda et al 2011, Petersson & Fransén 2012) and tests of peptides that interfere with TRP channel function (Yan et al 2009, Zhang et al 2011). However, thus far no direct evidence has demonstrated that persistent firing and the associated afterdepolarization response are abolished in TRP channel knockout animals [although Lei et al (2014) found partial blockade in TRPM5 knockout mice].…”

“…However, thus far no direct evidence has demonstrated that persistent firing and the associated afterdepolarization response are abolished in TRP channel knockout animals [although Lei et al (2014) found partial blockade in TRPM5 knockout mice]. Given the wide diversity of TRP channels (Reboreda et al 2011), fully testing this hypothesis may require generating mice that are null for many different TRP subunits.…”

Physiological Function and Characterization of TRPCs in Neurons

“…Ca 2+ also acts as a ubiquitous secondary messenger to modulate neuronal functions and also plays an important role in the relay of information via membrane depolarization [4,49,50]. TRPCs are predominantly expressed in neuronal cells and, thus, could be prime contributors in regulating fundamental neuronal functions via regulating the Ca 2+ flux in these neuronal cells [50].…”

“…Too much or too little Ca 2+ can be deadly to these neurons, so the Ca 2+ levels are carefully controlled in and outside of the cell. Such disturbances in Ca 2+ homeostasis have been involved in neurodegenerative diseases, such as Parkinson’s, Alzheimer’s and Huntington’s [2,3], which is mainly due to the high dependence of Ca 2+ signaling in various neuronal cells essential for their function [4]. Ca 2+ mobilization in neuronal cells is tightly regulated by different Ca 2+ channels and pumps in the plasma membrane and in the organelle membranes.…”