Dataset Information

Excitatory actions of peptide histidine isoleucine on thalamic relay neurons.

ABSTRACT: Peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) are neuropeptides synthesized from a common precursor, prepro-VIP, and share structural similarity and biological functions in many systems. Within the central nervous system and peripheral tissues, PHI and VIP have overlapping distribution. PHI-mediated functions are generally via activation of VIP receptors; however, the potency and affinity of PHI for VIP receptors are significantly lower than VIP. In addition, several studies suggest distinct PHI receptors that are independent of VIP receptors. PHI receptors have been cloned and characterized in fish, but their existence in mammals is still unknown. This study focuses on the functional role of PHI in the thalamus because of the localization of both PHI and VIP receptors in this brain region. Using extracellular multiple-unit recording techniques, we found that PHI strongly attenuated the slow intrathalamic rhythmic activity. Using intracellular recording techniques, we found that PHI selectively depolarized thalamic relay neurons via an enhancement of the hyperpolarization-activated mixed cation current, Ih. Further, the actions of PHI were occluded by VIP and dopamine, indicating these modulators converge onto a common mechanism. In contrast to previous work, we found that PHI was more potent than VIP in producing excitatory actions on thalamic neurons. We next used the transgenic mice lacking a specific VIP receptor, VPAC2, to identify its possible role in PHI-mediated actions in the thalamus. PHI depolarized all relay neurons tested from wild-type mice (VPAC2(+/+)); however, in knockout mice (VPAC2(-/-)), PHI produced no change in membrane potential in all neurons tested. Our findings indicate that excitatory actions of PHI are mediated by VPAC2 receptors, not by its own PHI receptors and the excitatory actions of PHI clearly attenuate intrathalamic rhythmic activities, and likely influence information transfer through thalamocortical circuits.

SUBMITTER: Lee SH

PROVIDER: S-EPMC2645485 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Excitatory actions of peptide histidine isoleucine on thalamic relay neurons.

Lee Sang-Hun SH Cox Charles L CL

Neuropharmacology 20080830 8

Peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) are neuropeptides synthesized from a common precursor, prepro-VIP, and share structural similarity and biological functions in many systems. Within the central nervous system and peripheral tissues, PHI and VIP have overlapping distribution. PHI-mediated functions are generally via activation of VIP receptors; however, the potency and affinity of PHI for VIP receptors are significantly lower than VIP. In addition, several ...[more]

PMID: 18804119

Similar Datasets

Project description:Relay cells are prevalent throughout sensory systems and receive two types of inputs: driving and modulating. The driving input contains receptive field properties that must be transmitted while the modulating input alters the specifics of transmission. For example, the visual thalamus contains relay neurons that receive driving inputs from the retina that encode a visual image, and modulating inputs from reticular activating system and layer 6 of visual cortex that control what aspects of the image will be relayed back to visual cortex for perception. What gets relayed depends on several factors such as attentional demands and a subject's goals. In this paper, we analyze a biophysical based model of a relay cell and use systems theoretic tools to construct analytic bounds on how well the cell transmits a driving input as a function of the neuron's electrophysiological properties, the modulating input, and the driving signal parameters. We assume that the modulating input belongs to a class of sinusoidal signals and that the driving input is an irregular train of pulses with inter-pulse intervals obeying an exponential distribution. Our analysis applies to any [Formula: see text] order model as long as the neuron does not spike without a driving input pulse and exhibits a refractory period. Our bounds on relay reliability contain performance obtained through simulation of a second and third order model, and suggest, for instance, that if the frequency of the modulating input increases or the DC offset decreases, then relay increases. Our analysis also shows, for the first time, how the biophysical properties of the neuron (e.g. ion channel dynamics) define the oscillatory patterns needed in the modulating input for appropriately timed relay of sensory information. In our discussion, we describe how our bounds predict experimentally observed neural activity in the basal ganglia in (i) health, (ii) in Parkinson's disease (PD), and (iii) in PD during therapeutic deep brain stimulation. Our bounds also predict different rhythms that emerge in the lateral geniculate nucleus in the thalamus during different attentional states.

Project description:A key feature of excitatory synapses is the existence of subsynaptic protein nanoclusters whose precise alignment across the cleft in a trans-synaptic nanocolumn influences the strength of synaptic transmission. However, whether nanocolumn properties vary between excitatory synapses functioning in different cellular contexts is unknown. We used a combination of confocal and DNA-PAINT super-resolution microscopy to directly compare the organization of shared scaffold proteins at two important excitatory synapses - those forming onto excitatory principal neurons (Ex→Ex synapses) and those forming onto parvalbumin-expressing interneurons (Ex→PV synapses). As in Ex→Ex synapses, we find that in Ex→PV synapses presynaptic Munc13-1 and postsynaptic PSD-95 both form nanoclusters that demonstrate alignment, underscoring synaptic nanostructure and the trans-synaptic nanocolumn as conserved organizational principles of excitatory synapses. Despite the general conservation of these features, we observed specific differences in the characteristics of pre- and postsynaptic Ex→PV nanostructure. Ex→PV synapses contained larger PSDs with fewer PSD-95 NCs when accounting for size than Ex→Ex synapses. Furthermore, the PSD-95 NCs were larger and denser. The identity of the postsynaptic cell also had a retrograde impact on Munc13-1 organization, as Ex→PV synapses hosted larger Munc13-1 puncta that contained less dense but larger and more numerous Munc13-1 NCs. Moreover, we measured the spatial variability of transsynaptic alignment in these synapse types, revealing protein alignment in Ex→PV synapses over a distinct range of distances compared to Ex→Ex synapses. We conclude that while general principles of nanostructure and alignment are shared, cell-specific elements of nanodomain organization likely contribute to functional diversity of excitatory synapses. Understanding the rules of synapse nanodomain assembly, which themselves are cell-type specific, will be essential for illuminating brain network dynamics.

Dataset Information

Excitatory actions of peptide histidine isoleucine on thalamic relay neurons.

Publications

Excitatory actions of peptide histidine isoleucine on thalamic relay neurons.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets