Subcellular Localization and Activity of TRPM4 in Medial Prefrontal Cortex Layer 2/3

Abstract

TRPM4 is a Ca2+-activated non-selective cationic channel that conducts monovalent cations. TRPM4 has been proposed to contribute to burst firing and sustained activity in several brain regions, however, the cellular and subcellular pattern of TRPM4 expression in medial prefrontal cortex (mPFC) during postnatal development has not been elucidated. Here, we use multiplex immunofluorescence labeling of brain sections to characterize the postnatal developmental expression of TRPM4 in the mouse mPFC. We also performed electrophysiological recordings to correlate the expression of TRPM4 immunoreactivity with the presence of TRPM4-like currents. We found that TRPM4 is expressed from the first postnatal day, with expression increasing up to postnatal day 35. Additionally, in perforated patch clamp experiments, we found that TRPM4-like currents were active at resting membrane potentials at all postnatal ages studied. Moreover, TRPM4 is expressed in both pyramidal neurons and interneurons. TRPM4 expression is localized in the soma and proximal dendrites, but not in the axon initial segment of pyramidal neurons. This subcellular localization is consistent with a reduction in the basal current only when we locally perfused 9-Phenanthrol in the soma, but not upon perfusion in the medial or distal dendrites. Our results show a specific localization of TRPM4 expression in neurons in the mPFC and that a 9-Phenanthrol sensitive current is active at resting membrane potential, suggesting specific functional roles in mPFC neurons during postnatal development and in adulthood.

Parameter tuning differentiates granule cell subtypes enriching the repertoire of retransmission properties at the cerebellum input stage

“…In excitable cells, it is regarded as the most suitable signaling mechanism to boost the depolarizing drive following an increase in electrical activity, which reflects into the activation of voltage-gated Ca 2+ channels (Petersen, 2002). Emerging evidence showed that TRPM4 is actually recruited by an increase in cytosolic Ca 2+ concentration to generate a DISC current and finely tune neuronal excitability in several brain areas (Lei et al, 2014;Menigoz et al, 2016;Riquelme et al, 2018). For instance, TRPM4 mediates the depolarizing afterpotential and phasic bursting observed in supraoptic and periventricular nuclei of the hypothalamus after a train of action potentials (Teruyama et al, 2011) and contributes to increase the firing rate in PCs (Kim et al, 2013).…”

Glia-Derived Extracellular Vesicles in Parkinson’s Disease

“…A key aspect of PD pathophysiology is neuroinflammation in the SNpc, where reactive astrocytes and microglia intersect the key cellular functions affected in PD, namely, oxidative stress and the inflammatory response, endoplasmic reticulum (ER) stress, mitochondrial, lysosomal, proteosomal and autophagic functions, converging to α-Syn aggregation and prion-like cell-to-cell transmission of α-Syn [ 25 , 74 , 75 , 76 , 77 ].…”

TRP Channels Regulation of Rho GTPases in Brain Context and Diseases

“…Despite that, TRPM4 regulates Ca 2+ signals in different cell types, such as fibroblasts (Cáceres et al, 2015), mastocytes (Shimizu et al, 2009), dendritic cells (Barbet et al, 2008), and lymphocytes (Launay et al, 2004). TRPM4 expression has been described in hypothalamus (Teruyama et al, 2011), hippocampal CA1 area (Menigoz et al, 2016), preBötzinger nucleus (Picardo et al, 2019), and medial prefrontal cortex (Riquelme et al, 2018). Interestingly, TRPM4 increases Rac1 activity in MEF cells (Cáceres et al, 2015).…”

“…These features and the wide expression of these channels in multiple tissues and cell types, grant a high level of complexity to their role in diverse physiological and pathophysiological processes ( Venkatachalam and Montell, 2007 ). In this context, several TRP channels are implicated in cellular processes related to central nervous system (CNS) functioning such as the modulation of neuronal excitability ( Mickle et al, 2016 ; Hong et al, 2020b ), maturation or establishment of subcellular structures such as dendrites ( Tai et al, 2008 ), excitatory synapses ( Zhou et al, 2008 ), axonal outgrowth ( Jang et al, 2014 ), frontal cortex postnatal development ( Riquelme et al, 2018 ) and brain blood flow regulation ( Earley et al, 2004 ; Cornillot et al, 2019 ). Also, current evidence suggests that TRP channels could regulate downstream processes such as gene expression or more lasting effects, like Long Term Potentiation (LTP).…”