Excitatory actions of substance P in the rat lateral posterior nucleus

Abstract

The lateral posterior nucleus (LP) receives inputs from both neocortex and superior colliculus (SC), and is involved with integration and processing of higher-level visual information. Relay neurons in LP contain tachykinin receptors and are innervated by substance P (SP)-containing SC neurons and by layer V neurons of the visual cortex. In this study, we investigated the actions of SP on LP relay neurons using whole-cell recording techniques. SP produced a graded depolarizing response in LP neurons along the rostro-caudal extent of the lateral subdivision of LP nuclei (LPl), with a significantly larger response in rostral LPl neurons compared with caudal LPl neurons. In rostral LPl, SP (5-2000 nm) depolarized nearly all relay neurons tested (> 98%) in a concentration-dependent manner. Voltage-clamp experiments revealed that SP produced an inward current associated with a decreased conductance. The inward current was mediated primarily by neurokinin receptor (NK)(1) tachykinin receptors, although significantly smaller inward currents were produced by specific NK2 and NK3 receptor agonists. The selective NK(1) receptor antagonist RP67580 attenuated the SP-mediated response by 71.5% and was significantly larger than the attenuation of the SP response obtained by NK2 and NK3 receptor antagonists, GR159897 and SB222200, respectively. The SP-mediated response showed voltage characteristics consistent with a K+ conductance, and was attenuated by Cs+, a K+ channel blocker. Our data suggest that SP may modulate visual information that is being processed and integrated in the LPl with inputs from collicular sources.

Postnatal development of synaptic properties of the GABAergic projection from the inferior colliculus to the auditory thalamus

“…Concentrations of extracellular and intracellular solutions were adapted from Paul and Cox (2010). The intracellular solution consisted of (in mM) 120 K-gluconate, 4 KCl, 1 MgCl 2 , 0.07 CaCl 2 , 0.1 EGTA, 10 HEPES, 2 disodium ATP, and 0.4 sodium GTP with 0.03-0.05% Neurobiotin (pH of 7.2 and osmolarity of 290 mosM).…”

Substance P and the tectothalamic pathway.

“…In the LPN, a recent study demonstrated that SP reduces a K+ conductance, likely Kleak, via NKI receptors (Paul and Cox, 2010). The increases in input resistance that we identified following bath application of SP or high frequency stimulation of the SC are consistent with this action.…”

“…The effects of SP on membrane conductance in the LPN have been shown to be mediated by potassium channels, specifically potassium leak (K 1eak ) channels (Paul and Cox, 2010). A decrease in the conductance of K 1eak would increase membrane resistance and depolarize the cell.…”

“…The NKI receptor is associated with excitatory activity in many areas of central nervous system (Go and Yaksh, 1987, Adelson et aI., 2009, Paul and Cox, 2010 and has been shown to undergo endosomal internalization in the presence of SP (Mantyh et aI., 1995). Many G protein-coupled receptors exhibit internalization as part of their signaling sequence.…”

Frequency-Dependent Release of Substance P Mediates Heterosynaptic Potentiation of Glutamatergic Synaptic Responses in the Rat Visual Thalamus

“…However, although a number of studies have demonstrated that the membrane properties of thalamic neurons can be significantly altered by the exogenous application of neuropeptides (Brill et al 2007;Cox et al 1997;Govindaiah and Cox 2006;Cox 2006, 2008;Paul and Cox 2010;Sun et al 2002) or by their release from intrinsic interneurons (Sun et al 2003), little is known regarding the conditions under which neuropeptides are released by extrinsic inputs to the thalamus or their effects on neuronal responses to conventional neurotransmitters. This is an important avenue of investigation because the ability to manipulate thalamic synaptic efficacy could be used to modify abnormal thalamic activity patterns that occur in conditions such as epilepsy or neuropathic pain.…”