Differential alterations of intracellular [Ca2+] dynamics induced by cocaine and methylphenidate in thalamocortical ventrobasal neurons

Abstract

The ventrobasal (VB) thalamus relay nucleus processes information from rodents’ whiskers, projecting to somatosensory cortex. Cocaine and methylphenidate (MPH) have been described to differentially alter intrinsic properties of, and spontaneous GABAergic input to, VB neurons. Here we studied using bis-fura 2 ratiometric fluorescence the effects of cocaine and MPH on intracellular [Ca2+] dynamics at the soma and dendrites of VB neurons. Cocaine increased baseline fluorescence in VB somatic and dendritic compartments. Peak and areas of fluorescence amplitudes were reduced by cocaine binge treatment in somas and dendrites at different holding potentials. MPH binge treatment did not alter ratiometric fluorescence at either somatic or dendritic levels. These novel cocaine-mediated blunting effects on intracellular [Ca2+] might account for alterations in the capacity of thalamocortical neurons to maintain gamma band oscillations, as well as their ability to integrate synaptic afferents.

Simultaneous administration of cocaine and caffeine dysregulates HCN and T-type channels

“…On the other hand, it has been reported that an acute cocaine dose (1 mg/kg) induced in vivo a large increase of [Ca 2+ ] i in the cortex of the rat brain (Du et al 2006). Similarly, VB neurons exhibited high levels of [Ca 2+ ] i 1-h after an acute cocaine administration (3 injections, 15 mg/kg each, 1 h apart) (Rozas et al 2017). However, our experiments were performed 24-h after the acute cocaine administration.…”

“…To allow sufficient intarcellular filling of VB neurons with dye, imaging was initiated 5-10 min after obtaining whole-cell configuration. The ratiometric Ca 2+ -sensitive indicator fura-2 (in vitro K d = 224 nM) allowed a more accurate report of the time course and amplitude of intracellular [Ca 2+ ] dynamics at somatic and proximal dendrites level (Rozas et al 2017). Fluorescence changes at 510 nm were acquired after consecutive 340 nm and 380 nm wavelengths using a 0.8 numerical aperture water-immersion 40× objective (Olympus Latin America Inc., FL, USA).…”

“…Acute "PACO"-like binge administration alters intracellular calcium dynamics To further confirm our findings, we investigated whether acute "PACO"-like binges lead to detectable changes in intracellular Ca 2+ concentration. Ratiometric Fura-2-based calcium imaging was performed concurrently with wholecell recordings in VB neurons (Di Guilmi et al 2014;Rozas et al 2017;Rankovic et al 2010). We determined the basal [Ca 2+ ] i and used an inhibitory current step (− 200 pA for 500 ms) to measure Ca 2+ transients (LTS) associated to Hand T-type currents (Fig.…”