Modulation of in vivo GABA-evoked responses by nitric oxide-active compounds in the globus pallidus of rat

Abstract

Nitric oxide (NO) is a gaseous molecule acting as a messenger in both the peripheral and the central nervous systems. NO affects synaptic activity by modulating neurotransmitter release and/or receptor function. We previously observed that NO-active compounds modify the bioelectric activity of basal ganglia (BG) units. In this study, we applied microiontophoresis to extracellular in vivo recordings to investigate the effect of NO-active compounds on GABA-evoked responses in the globus pallidus (GP) of anesthetized rats. The changes induced by NO-active drugs on the GABA-induced inhibition were used as indicators of NO modulation. The response to GABA release was tested on recorded GP neurons before and during the administration of S-nitroso-glutathione (SNOG, a NO donor) and/or Nω-nitro-L: -arginine methyl ester (L: -NAME), an inhibitor of nitric oxide synthase (NOS); furthermore, SNOG and L: -NAME were tested at different ejection currents in order to highlight the possibility of a current-dependent effect in the nitrergic modulation of GABA transmission. In general, during SNOG ejection the magnitude of GABA-evoked responses was reduced, whereas the administration of L: -NAME produced the opposite effect. The results suggest that NO-active drugs modulate the response of GP neurons to GABA transmission; the effects induced by SNOG and L: -NAME were strictly related to the ejection currents. Then, the modulation of GABAergic transmission by NO could represent a mechanism to finely regulate the GP neurons activity with important consequences on the overall BG function.

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

“…Therefore, the modulatory action of indicaxanthin occurred in a peculiar synaptic environment, more finely regulated, possibly underlying the increase in discharge frequency. Interestingly, in our previous researches the striatum already showed its particularity, given that the microiontophoretic administration of nitric oxide donors, likely intervening in glutamatergic and GABAergic transmission, induced excitation in all basal ganglia structures, except for the striatum where inhibition was observed (Sardo et al, 2003 , 2006 , 2009 , 2011 ; Carletti et al, 2009 , 2012 ).…”

“…Indeed, indicaxanthin released from a barrel in 5 min at 60 nA was equivalent to 0.1 μl, corresponding approximatively to 0.34 ng (for 12 μM), 0.17 ng (for 6 μM), and 0.085 ng (for 3 μM). Apart from brain localization, microiontophoretic recordings were carried out in telencepahalic and diencephalic regions (cortex, hippocampus, striatum, globus pallidus, thalamus and subthalamic nucleus), involved in cognitive processes and mostly investigated by our group in previous electrophysiological researches (Sardo et al, 2003 , 2006 , 2009 , 2012 ; Carletti et al, 2012 , 2017 ; Plescia et al, 2014 ). Hindbrain areas were not taken in consideration for recordings because of stereotaxic limitations.…”

Nitric oxide regulates the firing rate of neuronal subtypes in the guinea pig ventral cochlear nucleus

“…To test this hypothesis, we have used the iontophoretic application of a NOS inhibitor and two NO donors, while recording from identified single units in vivo. For the inhibitor we used L-NAME which is a water-soluble, non-selective inhibitor that is suitable for iontophoresis (Carletti, Ferraro, Rizzo, Friscia, & Sardo, 2012). Initially, we used SIN-1 as an NO donor as it has often been used successfully for in vivo studies in the past (Galati et al, 2008).…”

“…The peroxynitrite can then either oxidize sensitive cellular components or lead to an active intermediate by reacting with glutathione to produce SNOG which can then release NO to activate guanylyl cyclase (Schrammel, Pfeiffer, Schmidt, Koesling, & Mayer, 1998). Thus we also used the iontophoresis of SNOG directly as it has been shown to be an effective source of NO when iontophoresed onto neurones in other parts of the brain (Carletti et al, 2012).…”

Baclofen or nNOS inhibitor affect molecular and behavioral alterations evoked by traumatic spinal cord injury in rat spinal cord

“…This signaling molecule affects synaptic activity by modulating neurotransmitter release and/or receptor function [1]. Although, NO has been established as a biological mediator of clinical relevance, its role in motor dysfunction, disturbances in the blood-spinal cord barrier function, edema formation, and cell injury is still not well understood.…”