ABSTRACT
Hyperpolarisation-activated (Ih) currents are considered important for dendritic integration, synaptic transmission, setting membrane potential and rhythmic action potential (AP) discharge in neurons of the central nervous system. Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels underlie these currents and are composed of homo- and hetero-tetramers of HCN channel subunits (HCN1-4), which confer distinct biophysical properties on the channel. Despite understanding the structure-function relationships of HCN channels with different subunit stoichiometry, our knowledge of their expression in defined neuronal populations remains limited. Recently, we have shown that HCN subunit expression is a feature of a specific population of dorsal horn interneurons that exhibit high-frequency AP discharge. Here we expand on this observation and use neuroanatomical markers to first identify well-characterised neuronal populations in the lumbar spinal cord and hippocampus and subsequently determine whether HCN4 expression correlates with high-frequency AP discharge in these populations. In the spinal cord, HCN4 is expressed in several putative inhibitory interneuron populations including parvalbumin (PV)-expressing islet cells (84.1%; SD: ±2.87), in addition to all putative Renshaw cells and Ia inhibitory interneurons. Similarly, virtually all PV-expressing cells in the hippocampal CA1 subfield (93.5%; ±3.40) and the dentate gyrus (90.9%; ±6.38) also express HCN4. This HCN4 expression profile in inhibitory interneurons mirrors both the prevalence of Ih sub-threshold currents and high-frequency AP discharge. Our findings indicate that HCN4 subunits are expressed in several populations of spinal and hippocampal interneurons, which are known to express both Ih sub-threshold currents and exhibit high-frequency AP discharge. As HCN channel function plays a critical role in pain perception, learning and memory, and sleep as well as the pathogenesis of several neurological diseases, these findings provide important insights into the identity and neurochemical status of cells that could underlie such conditions.
Subject(s)
Action Potentials/physiology , Hippocampus/cytology , Interneurons/physiology , Potassium Channels/metabolism , Spinal Cord/cytology , Animals , Calbindins , Carrier Proteins/metabolism , Cell Count , Choline O-Acetyltransferase/metabolism , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels , In Vitro Techniques , Interneurons/classification , Male , Membrane Proteins/metabolism , Microscopy, Confocal , Parvalbumins/metabolism , Potassium Channels/genetics , Protein Kinase C/metabolism , Rats , Rats, Wistar , S100 Calcium Binding Protein G/metabolismABSTRACT
Perception of normal bodily sensations relies on the precise regulation of sensory information entering the dorsal horn of the spinal cord. Inhibitory, axoaxonic, synapses provide a mechanism for this regulation, but the source of these important inhibitory connections remains to be elucidated. This study shows that a subpopulation of spinal interneurons that expresses parvalbumin and have specific morphological, connectivity and functional characteristics are a likely source of the inhibitory inputs that selectivity regulate non-noxious tactile input in the spinal cord. Our findings suggest that a loss of normal function in parvalbumin positive dorsal horn neurons may result in the development of tactile allodynia, where non-painful stimuli gain the capacity to evoke the sensation of pain.
Subject(s)
Axons/physiology , Electrophysiological Phenomena/physiology , Gene Expression Regulation/physiology , Parvalbumins/metabolism , Posterior Horn Cells/physiology , Action Potentials , Animals , Antibodies , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Transgenic , Muscle Fibers, Fast-Twitch/metabolism , Parvalbumins/genetics , Patch-Clamp Techniques , Posterior Horn Cells/ultrastructure , Ultraviolet RaysABSTRACT
What implications do the new multilateral trade agreements have for health and well-being? The relationship needs to be understood in order to put trade and health objectives into proper perspective. This introductory article looks at some of the areas in which international trade and public health interact.
