Regulation Of Locomotor Behavior Research Articles

Purkinje cell hyperexcitability and depressive-like behavior in mice lacking erg3 (ether-à-go-go-related gene) K+ channel subunits.

Potassium channels stabilize the resting potential and neuronal excitability. Among them, erg (ether-à-go-go-related gene) K+ channels represent a subfamily of voltage-gated channels, consisting of erg1, erg2, and erg3 subunits; however, their subunit-specific neuronal functions in vivo are barely understood. To find erg3- and erg1-mediated functions, we generated global Kcnh7 (erg3) and conditional Kcnh2 (erg1) knockout mice. We found that erg3 channels stabilize the resting potential and dampen spontaneous activity in cerebellar Purkinje cells (PCs) and hippocampal CA1 neurons, whereas erg1 channels have suprathreshold functions. Lack of erg3 subunits induced hyperexcitability with increased action potential firing in PCs, but not in CA1 neurons. Notably, erg3 depletion caused depressive-like behavior with reduced locomotor activity, strongly decreased digging behavior, and shorter latencies to fall off a rotating wheel, while learning and memory remained unchanged. Our data show that erg K+ channels containing erg3 subunits mediate a neuronal subthreshold K+ current that plays important roles in the regulation of locomotor behavior in vivo.

Sperm function is required for suppressing locomotor activity of C. elegans hermaphrodites.

Sex differences in sex-shared behavior are common across various species. During mating, males transfer sperm and seminal fluid to females, which can affect female behavior. Sperm can be stored in the female reproductive tract for extended periods of time and used to fertilize eggs. However, the role of either sperm or embryo production in regulating female behavior is poorly understood. In the androdioecious nematode C. elegans, hermaphrodites produce both oocytes and sperm, enabling them to self-fertilize or mate with males. Hermaphrodites exhibit less locomotor activity compared to males, indicating sex difference in behavioral regulation. In this study, mutants defective in the sperm production and function were examined to investigate the role of sperm function in the regulation of locomotor behavior. Infertile hermaphrodites exhibited increased locomotor activity, which was suppressed after mating with fertile males. The results suggest that sperm, seminal fluid, or the presence of embryos are detected by hermaphrodites, leading to a reduction in locomotor activity. Additionally, females of closely related gonochoristic species, C. remanei and C. brenneri, exhibited reduced locomotor activity after mating. The regulation of locomotion by sperm function may be an adaptive mechanism that enables hermaphrodites lacking sperm or embryo to search for mates and allow females to cease their search for mates after mating.

The Effect of Pedal Peptide-Type Neuropeptide on Locomotor Behavior and Muscle Physiology in the Sea Cucumber Apostichopus japonicus.

Neuropeptides are endogenous active substances that are present in nervous tissues and participate in behavioral and physiological processes of the animal system. Locomotor behavior is basic to predation, escape, reproduction in animals, and neuropeptides play an important role in locomotion. In this study, the function of pedal peptide-type neuropeptide (PDP) in the process of locomotor behavior of the sea cucumber Apostichopus japonicus was evaluated. The locomotor behavior of A. japonicus was recorded by infrared camera before and after PDP administration, and muscle physiology was studied by ultra performance liquid chromatography and quadrupole time-off-light mass spectrometry (UPLC-Q-TOF-MS) to clarify the potential physiological mechanisms. The results showed that PDP enhanced the cumulative duration of moving significantly at the 7th h after injection, and reduced the mean and maximum velocity by 16.90 and 14.22% in A. japonicus. The data of muscle metabolomics suggested that some significantly changed metabolites were related to locomotor behavior of sea cucumbers. The decreases of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) might result in the increases of lysophosphatidylcholines (lysoPC) and lysophosphatidylethanolamine (lysoPE), and suggested the change of fluidity and permeability in the muscle cell membrane, which would affect the physiology and function of muscle cells, and finally alter the locomotor behavior. In addition, the increased level of arachidonic acid (ARA) might activate K+ ion channels and then affect the signaling of muscle cells, or promote the sensitivity of muscle cells to Ca2+ and then result in the contractility of longitudinal muscles in sea cucumbers. ARA was also involved in the linoleic acid metabolism which was the only pathway that disturbed significantly after PDP administration. In conclusion, PDP participated in the regulation of locomotor behavior in the sea cucumber, and the decreased PE and PC, increased lysoPC, lysoPE and ARA might be the potential physiological mechanisms that responsible for behavioral effects of PDP in A. japonicus.

Pharmacological identification of cholinergic receptor subtypes: modulation of locomotion and neural circuit excitability in Drosophila larvae

Acetylcholine (ACh) is an abundant neurotransmitter and neuromodulator in many species. In Drosophila melanogaster ACh is the neurotransmitter used in peripheral sensory neurons and is a primary excitatory neurotransmitter and neuromodulator within the central nervous system (CNS). The receptors that facilitate cholinergic transmission are divided into two broad subtypes: the ionotropic nicotinic acetylcholine receptors (nAChRs) and the metabotropic muscarinic acetylcholine receptors (mAChRs). This receptor classification is shared in both mammals and insects; however, both the pharmacological and functional characterization of these receptors within the Drosophila nervous system has lagged behind its mammalian model counterparts. In order to identify the impact of ACh receptor subtypes in regulating the performance of neural circuits within the larval CNS, we used a behavioral and electrophysiological approach to assess cholinergic modulation of locomotion and sensory-CNS-motor circuit excitability. We exposed intact and semi-intact 3rd instar larvae to ACh receptor agonists and antagonists to observe their roles in behavior and regulation of neural circuit excitability and to investigate AChR pharmacological properties in vivo. We combined this with targeted AChR RNAi-mediated knockdown to identify specific receptor subtypes facilitating ACh modulation of circuit efficacy. We identify a contribution by both mAChRs and nAChRs in regulation of locomotor behavior and reveal they play a role in modulation of the excitability of a sensory-CNS-motor circuit. We further reveal a conspicuous role for mAChR-A and mAChR-C in motor neurons in modulation of their input-output efficacy.

Noninvasive method to control the human spinal locomotor systems

The mechanism of interactions between receptor activation in the musculoskeletal system and stimulation of the spinal cord in the regulation of locomotor behavior was studied in healthy subjects. Afferent stimulation was tested for effect on the patterns of stepping movements induced by percutaneous stimulation of the spinal cord. A combination of percutaneous spinal cord stimulation and vibratory stimulation was shown to increase the amplitude of leg movements. It was demonstrated that vibratory stimulation of limb muscles at a frequency of less than 30 Hz can be used to control involuntary movements elicited by noninvasive stimulation of the spinal cord.

PDF receptor signaling in Caenorhabditis elegans modulates locomotion and egg-laying

In Caenorhabditis elegans, pdfr-1 encodes three receptors of the secretin receptor family. These G protein-coupled receptors are activated by three neuropeptides, pigment dispersing factors 1a, 1b and 2, which are encoded by pdf-1 and pdf-2. We isolated a PDF receptor loss-of-function allele (lst34) by means of a mutagenesis screen and show that the PDF signaling system is involved in locomotion and egg-laying. We demonstrate that the pdfr-1 mutant phenocopies the defective locomotor behavior of the pdf-1 mutant and that pdf-1 and pdf-2 behave antagonistically. All three PDF receptor splice variants are involved in the regulation of locomotor behavior. Cell specific rescue experiments show that this pdf mediated behavior is regulated by neurons rather than body wall muscles. We also show that egg-laying patterns of pdf-1 and pdf-2 mutants are affected, but not those of pdfr-1 mutants, pointing to a novel role for the PDF-system in the regulation of egg-laying.

Developmental expression of neuromodulators in the central complex of the grasshopper Schistocerca gregaria

The central complex is a major integrative region within the insect brain with demonstrated roles in spatial orientation, the regulation of locomotor behavior, and sound production. In the hemimetabolous grasshopper, the central complex comprises the protocerebral bridge, central body (CB), ellipsoid body, noduli, and accessory lobes, and this modular organization develops entirely during embryogenesis. From a biochemical perspective, a range of neuroactive substances has been demonstrated in these modules of the adult central complex, but little is known about their developmental expression. In this study, we use matrix-assisted laser desorption/ionization-imaging mass spectrometry on single brain slices to confirm the presence of several peptide families (tachykinin, allatostatin, periviscerokinin/pyrokinin, FLRFamide, and neuropeptide F) in the adult central complex and then use immunohistochemistry and histology to examine their developmental expression, together with that of the indolamin serotonin, and the endogenous messenger nitric oxide (NO; via its synthesizing enzyme). We find that each neuromodulator is expressed according to a unique, stereotypic, pattern within the various modules making up the central complex. Neuropeptides such as tachykinin (55%) and allatostatin (65%), and the NO-synthesizing enzyme diaphorase (70%), are expressed earlier during embryonic development than the biogenic amine serotonin (80%), whereas periviscerokinin-like peptides and FLRFamide-like peptides begin to be expressed only postembryonically. Within the CB, these neuroactive substances are present in tangential projection neurons before they appear in columnar neurons. There is also no colocalization of serotonin-positive and peptide-positive projections up to the third larval instar during development, consistent with the clear dorsoventral layering of the neuropil we observe. Our results provide the first neurochemical fingerprint of the developing central complex in an hemimetabolous insect.

Functional Characterization of Three G Protein-coupled Receptors for Pigment Dispersing Factors in Caenorhabditis elegans

Here, we report the identification, cloning, and functional characterization of three Caenorhabditis elegans G protein-coupled pigment dispersing factor (PDF) receptors, which we designated as Ce_PDFR-1a, -b, and -c. They represent three splice isoforms of the same gene (C13B9.4), which share a high degree of similarity with the Drosophila PDF receptor and are distantly related to the mammalian vasoactive intestinal peptide receptors (VPAC2) and calcitonin receptors. In a reverse pharmacological screen, three bioactive C. elegans neuropeptides, which were recently identified as the Drosophila PDF orthologues, were able to activate these receptors in a dose-dependent manner with nanomolar potency (isoforms a and b). Integrated green fluorescent protein reporter constructs reveal the expression of these PDF receptors in all body wall muscle cells and many head and tail neurons involved in the integration of environmental stimuli and the control of locomotion. Using a custom data analysis system, we demonstrate the involvement of this newly discovered neuropeptide signaling system in the regulation of locomotor behavior. Overexpression of PDF-2 phenocopies the locomotor defects of a PDF-1 null mutant, suggesting that they elicit opposite effects on locomotion through the identified PDF receptors. Our findings strengthen the hypothesis that the PDF signaling system, which imposes the circadian clock rhythm on behavior in Drosophila, has been functionally conserved throughout the protostomian evolutionary lineage.

Cellular and subcellular localization of the inhibitory glycine receptor in hippocampal neurons

Inhibitory glycine receptors are most abundant in spinal cord and brainstem, and glycinergic synapses have a well-established role in the regulation of locomotor behavior. Little is known about the function of glycine receptors in cortex and hippocampus, where GABA plays a dominant role in synaptic inhibition. Therefore, we have investigated tissue and cellular expression of glycine receptor α-subunits. Western blot and immunohistochemical analyses reveal the presence of glycine receptors in hippocampal tissue. Immunocytochemical experiments in hippocampal cultures show prominent cellular expression of glycine receptors in pyramidal neurons and GAD-positive interneurons similar to the calcium-binding protein VILIP-1 with widespread hippocampal distribution. On the subcellular level we found co-staining of GlyR and the presynaptic marker synapsin I. Furthermore, co-staining with GAD at synaptic terminals indicated partial co-localization of GABA- and glycine receptors.

Neuroactive steroids modulate crustacean locomotor activity

We examined the effects of neuroactive steroids known to modulate gamma-aminobutyric acid A (GABA) A receptor activity, on locomotor activity in a submerged circular open-field apparatus. Juvenile male lobsters, Homarus americanus, were treated with a single administration of an agonist, 3α-hydroxy-5α-pregnan-20-one (allopregnanolone, 3α,5α-TH PROG), an antagonist, pregnenolone sulfate (PREGS), or vehicle alone. 3α,5α-TH PROG treatment (125 and 250 μg) significantly reduced while PREGS significantly elevated locomotor activity in a dose-dependent manner similar to diazepam. PREGS increased locomotor activity at 30 and 60 μg, while diminishing such activity and altering locomotor patterns at 120 μg. These results suggest that neuroactive steroids may affect crustacean GABA receptors in a fashion similar to the GABA A type found in the vertebrates, and that they may be involved in the regulation of locomotor behavior.

The glycinergic inhibitory synapse.

Glycine is one of the most important inhibitory neurotransmitters in the spinal cord and the brainstem, and glycinergic synapses have a well-established role in the regulation of locomotor behavior. Research over the last 15 years has yielded new insights on glycine neurotransmission. Glycinergic synapses are now known not to be restricted to the spinal cord and the brainstem. Presynaptic machinery for glycine release and uptake, the structure and function of postsynaptic receptors and the factors (both pre- and postsynaptic) which control the strength of glycinergic inhibition have been extensively studied. It is now established that glycinergic synapses can be excitatory in the immature brain and that some inhibitory synapses can corelease gamma-aminobutyric acid (GABA) and glycine. Moreover, the presence of glycine transporters on glial cells and the capacity of these cells to release glycine suggest that glycine may also act as a neuromodulator. Extensive molecular studies have revealed the presence of distinct subtypes of postsynaptic glycine receptors with different functional properties. Mechanisms of glycine receptors aggregation at postsynaptic sites during development are better understood and functional implications of variation in receptor number between postsynaptic sites are partly elucidated. Mutations of glycine receptor subunits have been shown to underly some human locomotor disorders, including the startle disease. Clearly, recent work on glycine receptor channels and the synapses at which they mediate inhibitory signalling in both young and adult animals necessitates an update of our vision of glycinergic inhibitory transmission.