Action of substance P (neurokinin‐1) receptor activation on rat neostriatal projection neurons

Abstract

Substance P (SP) acts as a neurotransmitter in the neostriatum through the axon collaterals of spiny projection neurons. However, possible direct or indirect actions of SP on the neostriatal output neurons have not been described. Targets of SP terminals within the neostriatum include interneurons, spiny neurons, afferent fibers and boutons. SP induces the release of both dopamine (DA) and acetylcholine (ACh). Since some postsynaptic actions of both DA and ACh on spiny neurons are known, we asked if activation of neostriatal NK1-class receptors is able to reproduce them. The SP NK1-receptor agonist, GR73632 (1 microM), had both excitatory and inhibitory actions on virtually all spiny neurons tested at resting potential. The excitatory action was blocked by atropine and coursed with an increase in firing rate and input resistance (R(N)). The inhibitory action was blocked by haloperidol and coursed with a reduction in firing rate and R(N). Therefore, the release of both DA and ACh induced by NK1-receptor activation modulates indirectly the excitability of the projection neurons. SP facilitates the actions of these transmitters on the spiny neuron. A residual excitatory response to the NK1-receptor agonist was observed in 30% of a sample of neurons tested in the presence of both haloperidol and atropine. The increase in R(N) that accompanied this response could be observed in the presence of 1 microM TTX or 100 microM Cd2+, suggesting a direct effect. Double labeling showed that only SP-immunoreactive neurons were facilitated by NK1-receptor activation in these conditions.

Local circuit neurons in the striatum regulate neural and behavioral responses to dopaminergic stimulation

“…NK-1 receptors in the striatum are expressed principally by the cholinergic and NOS interneurons, but low levels of NK-1 receptor expression (22) and some direct NK-1 receptormediated effects (23) have been reported for SP-immunoreactive projection neurons themselves, suggesting the presence of NK-1 autoreceptors. We therefore tested for changes in the numbers of striatal projection neurons within the SP-PE35 injection sites.…”

A Reconfiguration of CaV2 Ca2+ Channel Current and Its Dopaminergic D2 Modulation in Developing Neostriatal Neurons

“…Briefly, and as described elsewhere (Bargas et al 1999), male Wistar rats of postnatal days 14 (PD14) and 40 (PD40), from our animal house, were deeply anesthetized, and their brains were quickly removed into ice-cold saline (4°C) containing (in mM) 126 NaCl, 3 KCl, 1 MgCl 2 , 2 CaCl 2 , 25 NaHCO 3 , and 11 glucose (pH 7.4 with NaOH, 298 mOsm/l with glucose; aerated with 95% O 2 -5% CO 2 ). Parasagittal neostriatal slices (300 m thick) were cut in 4°C saline using a vibratome (Ted Pella, Reading, CA).…”

“…Neostriatal neurons from PD14 or PD40 rats were acutely dissociated using procedures similar to those previously described (Bargas et al 1999). Briefly, after a 1-to 6-h incubation, slices were removed into HEPES-buffered saline, and the dorsal striatum was dissected.…”

“…Bridge balance as well as recovery periods (without DC current) were monitored between sample records. After recording, some neurons were injected with biocytin as previously described (Galarraga et al 1999). All neurons identified in this study were medium-sized spiny projection neurons.…”

“…In turn, these K ϩ channels generate the postspike afterhyperpolarization (AHP) that makes up the interspike interval. The AHP controls the firing of spiny cells by setting the gain for a given stimulus (Bargas et al 1999;Perez-Garci et al 2003;Pineda et al 1992;Vilchis et al 2000). In addition, Ca V 2 channels are in charge of GABA release at the synaptic terminals of spiny neurons .…”