Interplay between low threshold voltage-gated K(+) channels and synaptic inhibition in neurons of the chicken nucleus laminaris along its frequency axis.
Animals; IPSC; Chick Embryo; Patch-Clamp Techniques; Neurons/*physiology; Auditory Pathways/*physiology; GABAergic inhibition; Inhibitory Postsynaptic Potentials/*physiology; interaural time difference; IPSP; Sound Localization/physiology; Synaptic Transmission/*physiology; tonotopy; voltage-gated low-threshold potassium current; whole-cell patch; Potassium Channels; Voltage-Gated/*physiology
Central auditory neurons that localize sound in horizontal space have specialized intrinsic and synaptic cellular mechanisms to tightly control the threshold and timing for action potential generation. However, the critical interplay between intrinsic voltage-gated conductances and extrinsic synaptic conductances in determining neuronal output are not well understood. In chicken, neurons in the nucleus laminaris (NL) encode sound location using interaural time difference (ITD) as a cue. Along the tonotopic axis of NL, there exist robust differences among low, middle, and high frequency (LF, MF, and HF, respectively) neurons in a variety of neuronal properties such as low threshold voltage-gated K(+) (LTK) channels and depolarizing inhibition. This establishes NL as an ideal model to examine the interactions between LTK currents and synaptic inhibition across the tonotopic axis. Using whole-cell patch clamp recordings prepared from chicken embryos (E17-E18), we found that LTK currents were larger in MF and HF neurons than in LF neurons. Kinetic analysis revealed that LTK currents in MF neurons activated at lower voltages than in LF and HF neurons, whereas the inactivation of the currents was similar across the tonotopic axis. Surprisingly, blockade of LTK currents using dendrotoxin-I (DTX) tended to broaden the duration and increase the amplitude of the depolarizing inhibitory postsynaptic potentials (IPSPs) in NL neurons without dependence on coding frequency regions. Analyses of the effects of DTX on inhibitory postsynaptic currents led us to interpret this unexpected observation as a result of primarily postsynaptic effects of LTK currents on MF and HF neurons, and combined presynaptic and postsynaptic effects in LF neurons. Furthermore, DTX transferred subthreshold IPSPs to spikes. Taken together, the results suggest a critical role for LTK currents in regulating inhibitory synaptic strength in ITD-coding neurons at various frequencies.
Hamlet William R; Liu Yu-Wei; Tang Zheng-Quan; Lu Yong
Frontiers in neural circuits
2014
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3389/fncir.2014.00051" target="_blank" rel="noreferrer noopener">10.3389/fncir.2014.00051</a>
Ambient GABA-activated tonic inhibition sharpens auditory coincidence detection via a depolarizing shunting mechanism.
Animals; Chick Embryo; Patch-Clamp Techniques; Electric Stimulation; Neurons/*physiology; gamma-Aminobutyric Acid/*physiology; Membrane Potentials/physiology; Auditory Pathways/*physiology; Neural Inhibition/*physiology; Inhibitory Postsynaptic Potentials; Receptors; Blotting; Western; GABA-A/*physiology
Tonic inhibition mediated by extrasynaptic GABA(A) receptors (GABA(A)Rs) has emerged as a novel form of neural inhibition in the CNS. However, little is known about its presence and function in the auditory system. Using whole-cell recordings in brain slices, we identified a tonic current mediated by GABA(A)Rs containing the delta subunit in middle/high-characteristic-frequency neurons of the chicken nucleus laminaris, the first interaural time difference encoder that computes information for sound localization. This tonic conductance was activated by ambient concentrations of GABA released from synaptic vesicles. Furthermore, pharmacological manipulations of the conductance demonstrated its essential role in coincidence detection. Remarkably, this depolarizing tonic conductance was strongly inhibitory primarily because of its shunting effect. These results demonstrate a novel role for tonic inhibition in central auditory information processing.
Tang Zheng-Quan; Dinh Emilie Hoang; Shi Wei; Lu Yong
The Journal of neuroscience : the official journal of the Society for Neuroscience
2011
2011-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1523/JNEUROSCI.4733-10.2011" target="_blank" rel="noreferrer noopener">10.1523/JNEUROSCI.4733-10.2011</a>
Synaptic Inhibition in Avian Interaural Level Difference Sound Localizing Neurons.
Female; Male; Animals; Acoustic Stimulation/methods; Tissue Culture Techniques; Chick Embryo; Patch-Clamp Techniques; *dorsal nucleus of the lateral lemniscus; *GABAA receptor; *interaural level difference; *reversal potential; *synaptic inhibition; Anions/metabolism; Avian Proteins/metabolism; Brain Stem/cytology/drug effects/*physiology; Chlorides/metabolism; Electric Stimulation; gamma-Aminobutyric Acid/metabolism; Intracellular Space/drug effects/metabolism; Neural Inhibition/drug effects/*physiology; Neurons/cytology/drug effects/*physiology; Sound Localization/drug effects/*physiology; Symporters/metabolism; Synaptic Transmission/drug effects/*physiology; Receptors; GABA-A/metabolism; Glycine/metabolism
Synaptic inhibition plays a fundamental role in the neural computation of the interaural level difference (ILD), an important cue for the localization of high-frequency sound. Here, we studied the inhibitory synaptic currents in the chicken posterior portion of the dorsal nucleus of the lateral lemniscus (LLDp), the first binaural level difference encoder of the avian auditory pathway. Using whole-cell recordings in brain slices, we provide the first evidence confirming a monosynaptic inhibition driven by direct electrical and chemical stimulation of the contralateral LLDp, establishing the reciprocal inhibitory connection between the two LLDps, a long-standing assumption in the field. This inhibition was largely mediated by GABAA receptors; however, functional glycine receptors were also identified. The reversal potential for the Cl(-) channels measured with gramicidin-perforated patch recordings was hyperpolarizing (-88 mV), corresponding to a low intracellular Cl(-) concentration (5.2 mm). Pharmacological manipulations of KCC2 (outwardly Cl(-) transporter) activity demonstrate that LLDp neurons can maintain a low intracellular Cl(-) concentration under a high Cl(-) load, allowing for the maintenance of hyperpolarizing inhibition. We further demonstrate that hyperpolarizing inhibition was more effective at regulating cellular excitability than depolarizing inhibition in LLDp neurons.
Curry Rebecca J; Lu Yong
eNeuro
2016
2016-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1523/ENEURO.0309-16.2016" target="_blank" rel="noreferrer noopener">10.1523/ENEURO.0309-16.2016</a>
Development of GPCR modulation of GABAergic transmission in chicken nucleus laminaris neurons.
Animals; Patch-Clamp Techniques; *Synaptic Transmission; gamma-Aminobutyric Acid/*metabolism; Neurons/*metabolism; Brain/*cytology; Chickens/*metabolism; Synapses/metabolism; Receptors; G-Protein-Coupled/*metabolism; GABA-A/metabolism; GABA-B/metabolism; Metabotropic Glutamate/metabolism
Neurons in the nucleus laminaris (NL) of birds act as coincidence detectors and encode interaural time difference to localize the sound source in the azimuth plane. GABAergic transmission in a number of CNS nuclei including the NL is subject to a dual modulation by presynaptic GABA(B) receptors (GABA(B)Rs) and metabotropic glutamate receptors (mGluRs). Here, using in vitro whole-cell patch clamp recordings from acute brain slices of the chick, we characterized the following important but unknown properties pertaining to such a dual modulation: (1) emergence of functional GABA synapses in NL neurons; (2) the temporal onset of neuromodulation mediated by GABA(B)Rs and mGluRs; and (3) the physiological conditions under which GABA(B)Rs and mGluRs are activated by endogenous transmitters. We found that (1) GABA(A)R-mediated synaptic responses were observed in about half of the neurons at embryonic day 11 (E11); (2) GABA(B)R-mediated modulation of the GABAergic transmission was detectable at E11, whereas the modulation by mGluRs did not emerge until E15; and (3) endogenous activity of GABA(B)Rs was induced by both low- (5 or 10 Hz) and high-frequency (200 Hz) stimulation of the GABAergic pathway, whereas endogenous activity of mGluRs was induced by high- (200 Hz) but not low-frequency (5 or 10 Hz) stimulation of the glutamatergic pathway. Furthermore, the endogenous activity of mGluRs was mediated by group II but not group III members. Therefore, autoreceptor-mediated modulation of GABAergic transmission emerges at the same time when the GABA synapses become functional. Heteroreceptor-mediated modulation appears at a later time and is receptor type dependent in vitro.
Tang Zheng-Quan; Lu Yong
PloS one
2012
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1371/journal.pone.0035831" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0035831</a>
Endogenous mGluR activity suppresses GABAergic transmission in avian cochlear nucleus magnocellularis neurons.
2-Amino-5-phosphonovalerate/pharmacology; Amino Acids/pharmacology; Animals; Chickens/*physiology; Cochlear Nucleus/*cytology/*physiology; Electric Stimulation; Excitatory Amino Acid Antagonists/pharmacology; Excitatory Postsynaptic Potentials/physiology; GABA-B Receptor Agonists; GABA-B Receptor Antagonists; GABA-B/physiology; gamma-Aminobutyric Acid/*physiology; Glycine/analogs & derivatives/pharmacology; In Vitro Techniques; Kinetics; Membrane Potentials/drug effects; Metabotropic Glutamate/agonists/antagonists & inhibitors/*metabolism/physiology; Models; Neurological; Neurons/*physiology; Patch-Clamp Techniques; Receptors; Resorcinols/pharmacology; Synapses/physiology; Synaptic Transmission/*physiology; Xanthenes/pharmacology
GABAergic transmission in the avian cochlear nucleus magnocellularis (NM) of the chick is subject to modulation by gamma-aminobutyric acid type B (GABA(B)) autoreceptors. Here, I investigated modulation of GABAergic transmission in NM by metabotropic glutamate receptors (mGluRs) with whole cell recordings in brain slice preparations. I found that tACPD, a nonspecific mGluR agonist, exerted dose-dependent suppression on evoked inhibitory postsynaptic currents (eIPSCs) in NM neurons. At concentrations of 100 or 200 microM, tACPD increased the failure rate of GABAergic transmission. Agonists for group I (3,5-DHPG, 200 microM), group II (DCG-IV, 2 microM), and group III (L-AP4, 10 microM) mGluRs produced a significant reduction in the amplitude of eIPSCs and a significant increase in failure rate, indicating the involvement of multiple mGluRs in this modulation. The frequency, but not the amplitude, of miniature IPSCs (mIPSCs) was decreased significantly by 3,5-DHPG or DCG-IV. Neither frequency nor amplitude of mIPSCs was affected by L-AP4. mGluR antagonists LY341495 (20 microM) plus CPPG (10 microM) significantly increased the amplitude of eIPSCs, indicating that endogenous mGluR activity suppresses GABA release to NM neurons. Furthermore, blockage of mGluRs increased GABA-evoked discharges recorded under physiological Cl(-) concentrations, whereas tACPD (100 microM) eliminated them. The results indicate that mGluRs play important roles in achieving balanced excitation and inhibition in NM and preserving fidelity of temporal information encoded by NM neurons.
Lu Yong
Journal of neurophysiology
2007
2007-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.00883.2006" target="_blank" rel="noreferrer noopener">10.1152/jn.00883.2006</a>
Postinhibitory rebound neurons and networks are disrupted in retrovirus-induced spongiform neurodegeneration.
Action Potentials/physiology; Animals; Antigens/metabolism; auditory midbrain; Calcium/metabolism; env/metabolism; Experimental/physiopathology; Gene Products; Hearing Loss/physiopathology; Inferior Colliculi/physiopathology/virology; inferior colliculus; Leukemia; Leukemia Virus; Membrane Potentials/physiology; Mice; Microglia/physiology/virology; Murine/*physiology; Neural Pathways/physiopathology; Neurodegenerative Diseases/*physiopathology; Neuroglia/physiology/virology; Neurons/*physiology/virology; Patch-Clamp Techniques; postinhibitory rebound neurons; Proteoglycans/metabolism; Retroviridae Infections/*physiopathology/virology; retrovirus; Tissue Culture Techniques; Tumor Virus Infections/*physiopathology/virology; Voltage-Sensitive Dye Imaging; voltage-sensitive dyes
Certain retroviruses induce progressive spongiform motor neuron disease with features resembling prion diseases and amyotrophic lateral sclerosis. With the neurovirulent murine leukemia virus (MLV) FrCasE, Env protein expression within glia leads to postsynaptic vacuolation, cellular effacement, and neuronal loss in the absence of neuroinflammation. To understand the physiological changes associated with MLV-induced spongiosis, and its neuronal specificity, we employed patch-clamp recordings and voltage-sensitive dye imaging in brain slices of the mouse inferior colliculus (IC), a midbrain nucleus that undergoes extensive spongiosis. IC neurons characterized by postinhibitory rebound firing (PIR) were selectively affected in FrCasE-infected mice. Coincident with Env expression in microglia and in glia characterized by NG2 proteoglycan expression (NG2 cells), rebound neurons (RNs) lost PIR, became hyperexcitable, and were reduced in number. PIR loss and hyperexcitability were reversed by raising internal calcium buffer concentrations in RNs. PIR-initiated rhythmic circuits were disrupted, and spontaneous synchronized bursting and prolonged depolarizations were widespread. Other IC neuron cell types and circuits within the same degenerative environment were unaffected. Antagonists of NMDA and/or AMPA receptors reduced burst firing in the IC but did not affect prolonged depolarizations. Antagonists of L-type calcium channels abolished both bursts and slow depolarizations. IC infection by the nonneurovirulent isogenic virus Friend 57E (Fr57E), whose Env protein is structurally similar to FrCasE, showed no RN hyperactivity or cell loss; however, PIR latency increased. These findings suggest that spongiform neurodegeneration arises from the unique excitability of RNs, their local regulation by glia, and the disruption of this relationship by glial expression of abnormal protein.
Li Ying; Davey Robert A; Sivaramakrishnan Shobhana; Lynch William P
Journal of neurophysiology
2014
2014-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.00227.2014" target="_blank" rel="noreferrer noopener">10.1152/jn.00227.2014</a>
Activation of metabotropic glutamate receptor 1 dimers requires glutamate binding in both subunits.
Blotting; Calcium Channels/drug effects/metabolism; DNA/biosynthesis/genetics; Dose-Response Relationship; Drug; Fluorescent Antibody Technique; Genes; Glutamic Acid/*metabolism; Humans; Membrane Potentials/drug effects; Metabotropic Glutamate/genetics/*metabolism; myc/genetics; Patch-Clamp Techniques; Plasmids/genetics; Receptors; Signal Transduction/drug effects; Superior Cervical Ganglion/cytology/drug effects/metabolism; Sympathetic Nervous System/cytology/drug effects/metabolism; Western
Group I metabotropic glutamate receptors (mGluRs) form stable, disulfide-linked homodimers. Lack of a verifiably monomeric mGluR1 mutant has led to difficulty in assessing the role of dimerization in the molecular mechanism of mGluR1 activation. The related GABA(B) receptor exhibits striking intradimer cross talk (ligand binding at one subunit effectively produces G protein activation at the other), but it is unclear whether group I mGluRs exhibit analogous cross talk. Signaling of heterologously expressed mGluR1 was examined in isolated rat sympathetic neurons by measuring glutamate-mediated inhibition of native calcium currents. To examine mGluR1 activity when only one dimer subunit has access to glutamate ligand, wildtype mGluR1 was coexpressed with mGluR1 Y74A, a mutant with impaired glutamate binding, and the activity of the heterodimer (mutant/wild type) was examined. The mGluR1 Y74A mutant alone had a dose-response curve that was shifted by about 2 orders of magnitude. The half-maximal dose of glutamate shifted from 1.3 (wild-type mGluR1) to about 450 (mGluR1 Y74A) microM. However, the maximal effect was similar. Wild-type mGluR1 was expressed with excess Y74A mGluR1 to generate a receptor population consisting largely of mutant homodimers and mutant/wild-type heterodimers but without detectable wild-type homodimers. Under these conditions, no glutamate-mediated calcium current inhibition was observed below approximately 300 microM glutamate, although wild-type mGluR1 protein was detectable with immunofluorescence. These data suggest that mutant/wild-type heterodimeric receptors are inactive at ligand concentrations favoring glutamate association with receptor dimers at only one subunit.
Kammermeier Paul J; Yun June
The Journal of pharmacology and experimental therapeutics
2005
2005-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1124/jpet.104.073155" target="_blank" rel="noreferrer noopener">10.1124/jpet.104.073155</a>
Intrinsic plasticity induced by group II metabotropic glutamate receptors via enhancement of high-threshold KV currents in sound localizing neurons.
Acoustic Stimulation/methods; Action Potentials/drug effects/physiology; Animals; Auditory Pathways/drug effects/*physiology; Brain/drug effects/physiology; Chick Embryo; Glutamic Acid/metabolism; metabotropic glutamate receptor; Metabotropic Glutamate/agonists/*metabolism; neuromodulation; Neuronal Plasticity/drug effects/*physiology; Neurons/drug effects/*physiology; nucleus laminaris; Patch-Clamp Techniques; Potassium Channels; Potassium/metabolism; Protein Kinase C/metabolism; Receptors; Sound Localization/drug effects/*physiology; Tissue Culture Techniques; Type C Phospholipases/metabolism; voltage-gated potassium channel; Voltage-Gated/*metabolism
Intrinsic plasticity has emerged as an important mechanism regulating neuronal excitability and output under physiological and pathological conditions. Here, we report a novel form of intrinsic plasticity. Using perforated patch clamp recordings, we examined the modulatory effects of group II metabotropic glutamate receptors (mGluR II) on voltage-gated potassium (KV) currents and the firing properties of neurons in the chicken nucleus laminaris (NL), the first central auditory station where interaural time cues are analyzed for sound localization. We found that activation of mGluR II by synthetic agonists resulted in a selective increase of the high-threshold KV currents. More importantly, synaptically released glutamate (with reuptake blocked) also enhanced the high-threshold KV currents. The enhancement was frequency-coding region dependent, being more pronounced in low-frequency neurons compared to middle- and high-frequency neurons. The intracellular mechanism involved the Gbetagamma signaling pathway associated with phospholipase C and protein kinase C. The modulation strengthened membrane outward rectification, sharpened action potentials, and improved the ability of NL neurons to follow high-frequency inputs. These data suggest that mGluR II provides a feedforward modulatory mechanism that may regulate temporal processing under the condition of heightened synaptic inputs.
Hamlet W R; Lu Y
Neuroscience
2016
2016-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2016.03.010" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2016.03.010</a>
Regulation of glutamatergic and GABAergic neurotransmission in the chick nucleus laminaris: role of N-type calcium channels.
Animals; Auditory Pathways/cytology/drug effects/metabolism; Calcium Channel Blockers/pharmacology; Calcium Channels; Chick Embryo; Chickens; Cochlear Nucleus/cytology/drug effects/*metabolism; Excitatory Postsynaptic Potentials/drug effects/physiology; Functional Laterality/drug effects/physiology; gamma-Aminobutyric Acid/*metabolism; Glutamic Acid/*metabolism; N-Type/*metabolism; Neural Inhibition/physiology; Neurons/drug effects/metabolism; omega-Conotoxin GVIA/pharmacology; Organ Culture Techniques; Patch-Clamp Techniques; Rhombencephalon/cytology/*metabolism; Synaptic Transmission/drug effects/*physiology
Neurons in the chicken nucleus laminaris (NL), the third order auditory nucleus involved in azimuth sound localization, receive bilaterally segregated (ipsilateral vs contralateral) glutamatergic excitation from the cochlear nucleus magnocellularis and GABAergic inhibition from the ipsilateral superior olivary nucleus (SON). Here, I investigate the voltage-gated calcium channels (VGCCs) that trigger the excitatory and the inhibitory transmission in the NL. Whole-cell recordings were performed in acute brainstem slices. The excitatory transmission was predominantly mediated by N-type VGCCs, as the specific N-type blocker omega-Conotoxin-GVIA (omega-CTx-GVIA, 1-2.5 microM) inhibited excitatory postsynaptic currents (EPSCs) by approximately 90%. Blockers for P/Q- and L-type VGCCs produced no inhibition, and blockade of R-type VGCCs produced a small inhibition. In individual cells, the effect of each VGCC blocker on the EPSC elicited by activation of the ipsilateral input was the same as that on the EPSC elicited by activation of the contralateral input, and the two EPSCs had similar kinetics, suggesting physiological symmetry between the two glutamatergic inputs to single NL neurons. The inhibitory transmission in NL neurons was almost exclusively mediated by N-type VGCCs, as omega-CTx-GVIA (1 microM) produced a approximately 90% reduction of inhibitory postsynaptic currents, whereas blockers for other VGCCs produced no inhibition. In conclusion, N-type VGCCs play a dominant role in triggering both the excitatory and the inhibitory transmission in the NL, and the presynaptic VGCCs that mediate the two bilaterally segregated glutamatergic inputs to individual NL neurons are identical. These features may play a role in optimizing coincidence detection in NL neurons.
Lu Y
Neuroscience
2009
2009-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2009.09.013" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2009.09.013</a>
Localization and function of NK(3) subtype tachykinin receptors of layer V pyramidal neurons of the guinea-pig medial prefrontal cortex.
Animals; Autoradiography/methods; Dose-Response Relationship; Drug; Drug Interactions; Excitatory Amino Acid Antagonists/pharmacology; Excitatory Postsynaptic Potentials/drug effects/radiation effects; Guinea Pigs; In Vitro Techniques; Iodine Isotopes/pharmacokinetics; Male; Membrane Potentials/drug effects/physiology/radiation effects; Neurokinin B/analogs & derivatives/pharmacokinetics; Neurokinin-3/agonists/antagonists & inhibitors/*metabolism; Patch-Clamp Techniques; Peptide Fragments/pharmacology; Prefrontal Cortex/*cytology; Protein Binding/drug effects; Pyramidal Cells/drug effects/*metabolism; Quinolines/pharmacology; Quinoxalines/pharmacology; Receptors; Substance P/analogs & derivatives/pharmacology; Valine/analogs & derivatives/pharmacology
The NK(3) subtype of tachykinin receptor has been implicated as a modulator of synaptic transmission in several brain regions, including the cerebral cortex. The localization and expression of NK(3) receptors within the brain vary from species to species. In addition, the pharmacology of NK(3) receptor-specific antagonists shows significant species variability. Among commonly used animal models, the pharmacology of the guinea-pig NK(3) receptor most closely resembles that of the human NK(3) receptor. Here, we provide anatomical localization studies, receptor binding studies, and studies of the electrophysiological effects of NK(3) receptor ligands of guinea-pig cortex using two commercially available ligands, the NK(3) receptor peptide analog agonist senktide, and the quinolinecarboxamide NK(3) receptor antagonist SB-222,200. Saturation binding studies with membranes isolated from guinea-pig cerebral cortex showed saturable binding consistent with a single high affinity site. Autoradiographic studies revealed dense specific binding in layers II/III and layer V of the cerebral cortex. For electrophysiological studies, brain slices were prepared from prefrontal cortex of 3- to 14-day-old guinea pigs. Whole cell recordings were made from layer V pyramidal neurons. In current clamp mode with a K(+)-containing pipette solution, senktide depolarized the pyramidal neurons and led to repetitive firing of action potentials. In voltage clamp mode with a Cs(+)-containing pipette solution, senktide application produced an inward current and a concentration-dependent enhancement of the amplitude and the frequency of spontaneous excitatory postsynaptic potentials. The glutamatergic nature of these events was demonstrated by block by glutamate receptor antagonists. The effects of senktide were blocked by SB-222,200, an NK(3) receptor antagonist. Taken together, these results are consistent with a functional role for NK(3) receptors located on neurons in the cerebral cortex. In layer V pyramidal neurons of the medial prefrontal cortex, activation of the NK(3) receptor system plays an excitatory role in modulating synaptic transmission.
Simmons M A; Sobotka-Briner C D; Medd A M
Neuroscience
2008
2008-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2008.08.037" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2008.08.037</a>
Early development of intrinsic and synaptic properties of chicken nucleus laminaris neurons.
Action Potentials/physiology; Aging/physiology; Animals; Auditory Pathways/cytology/*embryology/physiology; Auditory Perception/physiology; Body Patterning/physiology; Brain Stem/cytology/*embryology/physiology; Cell Differentiation/*physiology; Chick Embryo; Chickens; Cochlear Nucleus/cytology/*embryology/physiology; Excitatory Postsynaptic Potentials/physiology; Neurons/cytology/*physiology; Patch-Clamp Techniques; Potassium Channels; Sound Localization/physiology; Synapses/*physiology/ultrastructure; Time Factors; Voltage-Gated/physiology
Onset of auditory brainstem responses in chickens takes place at about embryonic day 11/12 (E11/12). We investigated early development of neuronal properties of chicken nucleus laminaris neurons, the third-order auditory neurons critically involved in sound localization. Whole-cell patch recordings were performed in brainstem slices obtained at E10, E11, E12, E14, E16, and E18. At E18 neurons acquired an adult-like firing pattern in response to prolonged depolarizing current injections, with a single spike at the onset of the current injection followed by a plateau of membrane potential. At earlier ages, however, multiple spikes and/or subthreshold membrane potential oscillations were generated. We observed a \textgreaterthreefold reduction in input resistance from E10 to E18, and progressive changes in excitability properties, such as elevated threshold currents for spike generation, increased spike rising and falling rates, accompanied by reduced spike width and enhanced ability to follow high frequency inputs. Consistent with development of firing properties, the amplitude of voltage-gated potassium channel (Kv) currents increased by approximately threefold from E10 to E18, with a dramatic increase ( approximately ninefold) in the low threshold component. Excitatory postsynaptic potentials (EPSPs) were first recorded at E10, prior to and independent of the cochlear afferent inputs from the auditory nerve to the cochlear nucleus. EPSPs became markedly briefer in duration during the period studied. We conclude that the basic features of the key neuronal properties of NL neurons are well constructed during early development from E10 to E18.
Gao H; Lu Y
Neuroscience
2008
2008-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2008.01.059" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2008.01.059</a>
Synaptic activity-induced Ca(2+) signaling in avian cochlear nucleus magnocellularis neurons.
Animals; Calcium Signaling/*physiology; Chick Embryo; Chickens; Cochlear Nucleus/*metabolism; GABA-A/metabolism; Inhibitory Postsynaptic Potentials/physiology; Neurons/*metabolism; Organ Culture Techniques; Patch-Clamp Techniques; Receptors; Synapses/*metabolism; Synaptic Transmission/*physiology
Neurons of the avian cochlear nucleus magnocellularis (NM) receive glutamatergic inputs from the spiral ganglion cells via the auditory nerve and feedback GABAergic inputs primarily from the superior olivary nucleus. We investigated regulation of Ca(2+) signaling in NM neurons with ratiometric Ca(2+) imaging in chicken brain slices. Application of exogenous glutamate or GABA increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) in NM neurons. Interestingly,
Wang Lie-Cheng; Tang Zheng-Quan; Lu Yong
Neuroscience research
2012
2012-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neures.2011.11.004" target="_blank" rel="noreferrer noopener">10.1016/j.neures.2011.11.004</a>
Metabotropic glutamate and GABA receptors modulate cellular excitability and glutamatergic transmission in chicken cochlear nucleus angularis neurons.
*Cellular excitability; *GABA(B)R; *mGluR; *Neuromodulation; *Nucleus angularis; *Synaptic transmission; Action Potentials/drug effects; Animals; Chick Embryo; Cochlear Nucleus/cytology/*physiology; Excitatory Postsynaptic Potentials/drug effects; GABA-B Receptor Agonists/pharmacology; GABA-B/*physiology; Glutamic Acid/*physiology; Metabotropic Glutamate/agonists/classification/*physiology; Neurons/drug effects/physiology; Patch-Clamp Techniques; Receptors; Synaptic Transmission/drug effects
Neurons in the avian cochlear nucleus angularis (NA) receive glutamatergic input from the auditory nerve, and GABAergic input from the superior olivary nucleus. Physiologically heterogeneous, NA neurons perform multiple functions including encoding sound intensity information. Using in vitro whole-cell patch recordings from acute brain slices and immunohistochemistry staining, we investigated neuromodulation mediated by metabotropic glutamate and GABA receptors (mGluRs and GABABRs) in NA neurons. Based on their intrinsic firing patterns in response to somatic current injections, NA neurons were classified into onset, damped, and tonic cells. Pharmacological activation of group II mGluRs, group III mGluRs, and GABABRs, by their respective agonists, suppressed the cellular excitability of non-onset firing NA neurons. Each of these agonists inhibited the glutamatergic transmission in NA neurons, in a cell type-independent manner. The frequency but not the amplitude of spontaneous release of glutamate was reduced by each of these agonists, suggesting that the modulation of the glutamatergic transmission was via presynaptic actions. Interestingly, activation of group I mGluRs increased cellular excitability and suppressed glutamatergic transmission in non-onset neurons. These results elaborate that auditory processing in NA neurons is subject to neuromodulation mediated by metabotropic receptors activated by native neurotransmitters released at NA.
Shi Wei; Lu Yong
Hearing research
2017
2017-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.heares.2017.01.011" target="_blank" rel="noreferrer noopener">10.1016/j.heares.2017.01.011</a>
4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling.
*4-Hydroxynonenal; *Coronary regulation; *Lipid peroxidation; *Post-translational modification; *Protein Processing; *Reactive oxygen species; *Signal Transduction; *TRPV1; Action Potentials/drug effects; Aldehydes/antagonists & inhibitors/metabolism/*pharmacology; Animal; Animals; Blood Flow Velocity; Calcium Signaling/drug effects; Capsaicin/*pharmacology; Cardiovascular Agents/*pharmacology; Coronary Circulation/drug effects; Coronary Vessels/metabolism/physiopathology; Cysteine/genetics/metabolism; Diabetes Mellitus/drug therapy/*metabolism/physiopathology; Disease Models; Femoral Artery/metabolism/physiopathology; HEK293 Cells; Humans; Inbred C57BL; Lipid Peroxidation; Male; Mice; Patch-Clamp Techniques; Post-Translational; TRPV Cation Channels/genetics/*metabolism; Vasodilation/drug effects
We demonstrated previously that TRPV1-dependent regulation of coronary blood flow (CBF) is disrupted in diabetes. Further, we have shown that endothelial TRPV1 is differentially regulated, ultimately leading to the inactivation of TRPV1, when exposed to a prolonged pathophysiological oxidative environment. This environment has been shown to increase lipid peroxidation byproducts including
DelloStritto Daniel J; Sinharoy Pritam; Connell Patrick J; Fahmy Joseph N; Cappelli Holly C; Thodeti Charles K; Geldenhuys Werner J; Damron Derek S; Bratz Ian N
Free radical biology & medicine
2016
2016-12
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<a href="http://doi.org/10.1016/j.freeradbiomed.2016.09.021" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2016.09.021</a>