GABAB Receptor Activation Modulates GABAA Receptor-Mediated Inhibition in Chicken Nucleus Magnocellularis Neurons

2005 ◽  
Vol 93 (3) ◽  
pp. 1429-1438 ◽  
Author(s):  
Yong Lu ◽  
R. Michael Burger ◽  
Edwin W Rubel
Keyword(s):  
Low Voltage ◽  
Gabab Receptor ◽  
Receptor Activation ◽  
Excitatory Input ◽  
Inhibitory Input ◽  
Nucleus Magnocellularis ◽  
Postsynaptic Currents ◽  
Endogenous Gaba ◽  
Cell Recording ◽  
Temporal Encoding

Neurons of nucleus magnocellularis (NM), a division of avian cochlear nucleus that performs precise temporal encoding, receive glutamatergic excitatory input solely from the eighth nerve and GABAergic inhibitory input primarily from the ipsilateral superior olivary nucleus. GABA activates both ligand-gated Cl− channels [GABAA receptors (GABAARs)] and G protein-coupled receptors (GABAB receptors). The net effect of GABAAR-mediated input to NM is inhibitory, although depolarizing. Several studies have shown that this shunting, inhibitory GABAergic input can evoke action potentials in postsynaptic NM neurons, which could interfere with their temporal encoding. While this GABA-mediated firing is limited by a low-voltage-activated K+ conductance, we have found evidence for a second mechanism. We investigated modulation of GABAAR-mediated responses by GABABRs using whole cell recording techniques. Bath-applied baclofen, a GABABR agonist, produced dose-dependent suppression of evoked inhibitory postsynaptic currents (eIPSCs). This suppression was blocked by CGP52432 , a potent and selective GABABR antagonist. Baclofen reduced the frequency but not the amplitude of miniature IPSCs (mIPSCs) and did not affect postsynaptic currents elicited by puff application of a specific GABAAR agonist muscimol, suggesting a presynaptic mechanism for the GABABR-mediated modulation. Firing of NM neurons by synaptic stimulation of GABAergic inputs to NM was eliminated by baclofen. However, endogenous GABABR activity in the presynaptic inhibitory terminals was not observed. We propose that presynaptic GABABRs function as autoreceptors, regulating synaptic strength of GABAAR-mediated inhibition, and prevent NM neurons from generating firing during activation of the inhibitory inputs.

scholarly journals Noradrenergic and GABAB Receptor Activation Differentially Modulate Inputs to the Premotor Nucleus RA in Zebra Finches

2008 ◽  
Vol 100 (1) ◽  
pp. 8-18 ◽  
Author(s):  
Max Sizemore ◽  
David J. Perkel
Keyword(s):  
Gabab Receptor ◽  
Cell Voltage ◽  
Receptor Activation ◽  
Social Contexts ◽  
Excitatory Input ◽  
Song Learning ◽  
Zebra Finches ◽  
Proper Name ◽  
Magnocellular Nucleus

Neuromodulators can rapidly modify neural circuits, altering behavior. Songbirds provide an excellent system for studying the role of neuromodulation in modifying circuits that underlie behavior because song learning and production are mediated by a discrete set of interconnected nuclei. We examined the neuromodulatory effects of noradrenergic and GABAB receptor activation on synaptic inputs to the premotor robust nucleus of the arcopallium (RA) in zebra finches using whole cell voltage-clamp recording in vitro. In adults, norepinephrine strongly reduced input from the lateral magnocellular nucleus of the anterior nidopallium (LMAN) but only slightly reduced the input from nucleus HVC (proper name), the excitatory input from axon collaterals of other RA neurons, and input from GABAergic interneurons. The effect of norepinephrine was mimicked by the α2 adrenoceptor agonist UK14,304 and blocked by the α2 antagonist yohimbine. Conversely, the GABAB receptor agonist baclofen strongly decreased HVC, collateral, and GABAergic inputs to RA neurons while causing little reduction in the LMAN input. In juveniles undergoing song learning, norepinephrine reduced the LMAN input, caused only a small reduction in the HVC input, and greatly reduced the collateral and GABAergic inputs. Baclofen caused similar results in juvenile and adult birds, reducing HVC, collateral, and GABAergic inputs significantly more than the LMAN input. Significant increases in paired-pulse ratio accompanied all reductions in synaptic transmission, suggesting a presynaptic locus. The reduction in the LMAN input by norepinephrine may be important for mediating changes in song elicited by different social contexts and is well-placed to play a role in song learning.

Selective Modulation of Excitatory Transmission by μ-Opioid Receptor Activation in Rat Supraoptic Neurons

1999 ◽  
Vol 82 (6) ◽  
pp. 3000-3005 ◽  
Author(s):  
Qing-Song Liu ◽  
Sheng Han ◽  
You-Sheng Jia ◽  
Gong Ju
Keyword(s):  
Opioid Receptor ◽  
Amplitude Distribution ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Membrane Hyperpolarization ◽  
Postsynaptic Currents ◽  
Cell Recording ◽  
Μ Opioid Receptor ◽  
Neuroendocrine Neurons ◽  
Supraoptic Neurons

Opioid peptides have profound inhibitory effects on the production of oxytocin and vasopressin, but their direct effects on magnocellular neuroendocrine neurons appear to be relatively weak. We tested whether a presynaptic mechanism is involved in this inhibition. The effects of μ-opioid receptor agonist d-Ala2, N-CH3-Phe4, Gly5-ol-enkephalin (DAGO) on excitatory and inhibitory transmission were studied in supraoptic nucleus (SON) neurons from rat hypothalamic slices using whole cell recording. DAGO reduced the amplitude of evoked glutamatergic excitatory postsynaptic currents (EPSCs) in a dose-dependent manner. In the presence of tetrodotoxin (TTX) to block spike activity, DAGO also reduced the frequency of spontaneous miniature EPSCs without altering their amplitude distribution, rising time, or decaying time constant. The above effects of DAGO were reversed by wash out, or by addition of opioid receptor antagonist naloxone or selective μ-antagonist Cys2-Tyr3-Orn5-Pen7-NH2(CTOP). In contrast, DAGO had no significant effect on the evoked and spontaneous miniature GABAergic inhibitory postsynaptic currents (IPSCs) in most SON neurons. A direct membrane hyperpolarization of SON neurons was not detected in the presence of DAGO. These results indicate that μ-opioid receptor activation selectively inhibits excitatory activity in SON neurons via a presynaptic mechanism.

AMPA receptor kinetics limit retinal amacrine cell excitatory synaptic responses

1999 ◽  
Vol 16 (5) ◽  
pp. 835-842 ◽  
Author(s):  
MY N. TRAN ◽  
MATTHEW H. HIGGS ◽  
PETER D. LUKASIEWICZ
Keyword(s):  
Ampa Receptor ◽  
Amacrine Cell ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Receptor Activation ◽  
Bipolar Cells ◽  
Inhibitory Input ◽  
Receptor Desensitization ◽  
Receptor Kinetics ◽  
Postsynaptic Currents

Amacrine cells that respond transiently to maintained illumination are thought to mediate transient inhibitory input to ganglion cells. The excitation of these transient amacrine cells is thought to be limited by inhibitory feedback to bipolar cells. We investigated the possibility that desensitizing AMPA and/or kainate (KA) receptors on amacrine cells might also limit the duration of amacrine cell excitation. To determine how these receptors might affect amacrine cell input and output, we made whole-cell recordings from amacrine and ganglion cells in the salamander retinal slice. The specific AMPA receptor antagonist GYKI-53655 blocked non-NMDA receptor-mediated amacrine cell excitatory postsynaptic currents (EPSCs) and kainate puff-elicited currents, indicating that AMPA, and not KA, receptors mediated the responses. Cyclothiazide, an agent that reduces AMPA receptor desensitization, increased the amplitude and duration of amacrine cell EPSCs. To measure the output of transient amacrine cells, we recorded glycinergic inhibitory postsynaptic currents (IPSCs) from ganglion cells, and found that these were also enhanced by cyclothiazide. Thus, prolongation of amacrine cell AMPA receptor activation enhanced amacrine cell output. Current responses elicited by puffing glycine onto ganglion cell dendrites were not affected by cyclothiazide, indicating that the enhancement of glycinergic IPSCs was not due to a direct effect on glycine receptors. These data suggest that rapid AMPA receptor desensitization and/or deactivation limits glycinergic amacrine cell excitation and the resulting inhibitory synaptic output.

scholarly journals Intrinsic Dynamics in Neuronal Networks. I. Theory

2000 ◽  
Vol 83 (2) ◽  
pp. 808-827 ◽  
Author(s):  
P. E. Latham ◽  
B. J. Richmond ◽  
P. G. Nelson ◽  
S. Nirenberg
Keyword(s):  
Firing Rate ◽  
Firing Pattern ◽  
Neuronal Networks ◽  
Network Connectivity ◽  
Excitatory Input ◽  
High Rate ◽  
Inhibitory Neurons ◽  
Inhibitory Input ◽  
Dynamic Interactions ◽  
Firing Patterns

Many networks in the mammalian nervous system remain active in the absence of stimuli. This activity falls into two main patterns: steady firing at low rates and rhythmic bursting. How are these firing patterns generated? Specifically, how do dynamic interactions between excitatory and inhibitory neurons produce these firing patterns, and how do networks switch from one firing pattern to the other? We investigated these questions theoretically by examining the intrinsic dynamics of large networks of neurons. Using both a semianalytic model based on mean firing rate dynamics and simulations with large neuronal networks, we found that the dynamics, and thus the firing patterns, are controlled largely by one parameter, the fraction of endogenously active cells. When no endogenously active cells are present, networks are either silent or fire at a high rate; as the number of endogenously active cells increases, there is a transition to bursting; and, with a further increase, there is a second transition to steady firing at a low rate. A secondary role is played by network connectivity, which determines whether activity occurs at a constant mean firing rate or oscillates around that mean. These conclusions require only conventional assumptions: excitatory input to a neuron increases its firing rate, inhibitory input decreases it, and neurons exhibit spike-frequency adaptation. These conclusions also lead to two experimentally testable predictions: 1) isolated networks that fire at low rates must contain endogenously active cells and 2) a reduction in the fraction of endogenously active cells in such networks must lead to bursting.

Binaural processing of sound pressure level in the inferior colliculus

1987 ◽  
Vol 57 (4) ◽  
pp. 1130-1147 ◽  
Author(s):  
M. N. Semple ◽  
L. M. Kitzes
Keyword(s):  
Inferior Colliculus ◽  
Sound Pressure ◽  
Spatial Information ◽  
Discharge Rate ◽  
Excitatory Input ◽  
Central Nucleus ◽  
Intensity Difference ◽  
Inhibitory Input ◽  
Directional Information ◽  
Discharge Rates

The central auditory system could encode information about the location of a high-frequency sound source by comparing the sound pressure levels at the ears. Two potential computations are the interaural intensity difference (IID) and the average binaural intensity (ABI). In this study of the central nucleus of the inferior colliculus (ICC) of the anesthetized gerbil, we demonstrate that responses of 85% of the 97 single units in our sample were jointly influenced by IID and ABI. For a given ABI, discharge rate of most units is a sigmoidal function of IID, and peak rates occur at IIDs favoring the contralateral ear. Most commonly, successive increments of ABI cause successive shifts of the IID functions toward IIDs favoring the ipsilateral ear. Neurons displaying this behavior include many that would conventionally be classified EI (receiving predominantly excitatory input arising from one ear and inhibitory input from the other), many that would be classified EE (receiving predominantly excitatory input arising from each ear), and all that are responsive only to contralateral stimulation. The IID sensitivity of a very few EI neurons is unaffected by ABI, except near threshold. Such units could provide directional information that is independent of source intensity. A few EE neurons are very sensitive to ABI, but are minimally sensitive to IID. Nevertheless, our data indicate that responses of most EE units in ICC are strongly dominated by excitation of contralateral origin. For some units, discharge rate is nonmonotonically related to IID and is maximal when the stimuli at the two ears are of comparable sound pressure. This preference for zero IID is common for all binaural levels. Many EI neurons respond nonmonotonically to ABI. Discharge rates are greater for IIDs representative of contralateral space and are maximal at a single best ABI. For a subset of these neurons, the influence arising from the ipsilateral ear is comprised of a mixture of excitation and inhibition. As a consequence, discharge rates are nonmonotonically related not only to ABI but also to IID. This dual nonmonotonicity creates a clear focus of peak response at a particular ABI/IID combination. Because of their mixed monaural influences, such units would be ascribed to different classes of the conventional (EE/EI) binaural classification scheme depending on the binaural level presented. Several response classes were identified in this study, and each might contribute differently to the encoding of spatial information.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Circuit contributions to sensory-driven glutamatergic drive of olfactory bulb mitral and tufted cells during odorant inhalation

2021 ◽  
Author(s):  
Andrew K. Moran ◽  
Thomas P. Eiting ◽  
Matt Wachowiak
Keyword(s):  
Olfactory Bulb ◽  
Gabab Receptor ◽  
Glutamate Release ◽  
Excitatory Input ◽  
Slight Reduction ◽  
Receptor Antagonists ◽  
Glutamate Signaling ◽  
Inhibitory Circuits ◽  
Primary Determinant ◽  
Excitatory Drive

In the mammalian olfactory bulb (OB), mitral/tufted (MT) cells respond to odorant inhalation with diverse temporal patterns that are thought to encode odor information. Much of this diversity is already apparent at the level of glutamatergic input to MT cells, which receive direct, monosynaptic excitatory input from olfactory sensory neurons (OSNs) as well as multisynaptic excitatory drive via glutamatergic interneurons. Both pathways are also subject to modulation by inhibitory circuits in the glomerular layer of the OB. To understand the role of direct OSN input versus postsynaptic OB circuit mechanisms in shaping diverse dynamics of glutamatergic drive to MT cells, we imaged glutamate signaling onto MT cell dendrites in anesthetized mice while blocking multisynaptic excitatory drive with ionotropic glutamate receptor antagonists and blocking presynaptic modulation of glutamate release from OSNs with GABAB receptor antagonists. GABAB receptor blockade increased the magnitude of inhalation-linked glutamate transients onto MT cell apical dendrites without altering their inhalation-linked dynamics, confirming that presynaptic inhibition impacts the gain of OSN inputs to the OB. Surprisingly, blockade of multisynaptic excitation only modestly impacted glutamatergic input to MT cells, causing a slight reduction in the amplitude of inhalation-linked glutamate transients in response to low odorant concentrations and no change in the dynamics of each transient. Postsynaptic blockade also modestly impacted glutamate dynamics over a slower timescale, mainly by reducing adaptation of the glutamate response across multiple inhalations of odorant. These results suggest that direct glutamatergic input from OSNs provides the bulk of excitatory drive to MT cells, and that diversity in the dynamics of this input may be a primary determinant of the temporal diversity in MT cell responses that underlies odor representations at this stage.

scholarly journals Jacob, a Synapto-Nuclear Protein Messenger Linking N-methyl-D-aspartate Receptor Activation to Nuclear Gene Expression

2021 ◽  
Vol 13 ◽  
Author(s):  
Katarzyna M. Grochowska ◽  
Julia Bär ◽  
Guilherme M. Gomes ◽  
Michael R. Kreutz ◽  
Anna Karpova
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Protein Transport ◽  
Pyramidal Neurons ◽  
Temporal Integration ◽  
Dendritic Tree ◽  
Nuclear Gene ◽  
Receptor Activation ◽  
Excitatory Input ◽  
Splice Isoforms

Pyramidal neurons exhibit a complex dendritic tree that is decorated by a huge number of spine synapses receiving excitatory input. Synaptic signals not only act locally but are also conveyed to the nucleus of the postsynaptic neuron to regulate gene expression. This raises the question of how the spatio-temporal integration of synaptic inputs is accomplished at the genomic level and which molecular mechanisms are involved. Protein transport from synapse to nucleus has been shown in several studies and has the potential to encode synaptic signals at the site of origin and decode them in the nucleus. In this review, we summarize the knowledge about the properties of the synapto-nuclear messenger protein Jacob with special emphasis on a putative role in hippocampal neuronal plasticity. We will elaborate on the interactome of Jacob, the signals that control synapto-nuclear trafficking, the mechanisms of transport, and the potential nuclear function. In addition, we will address the organization of the Jacob/NSMF gene, its origin and we will summarize the evidence for the existence of splice isoforms and their expression pattern.

scholarly journals M4 Muscarinic Receptor Activation Modulates Calcium Channel Currents in Rat Intracardiac Neurons

1997 ◽  
Vol 78 (4) ◽  
pp. 1903-1912 ◽  
Author(s):  
J. Cuevas ◽  
D. J. Adams
Keyword(s):  
Calcium Channel ◽  
Muscarinic Receptor ◽  
High Voltage ◽  
Receptor Activation ◽  
Muscarinic Agonist ◽  
Muscarinic Agonists ◽  
Maximal Inhibition ◽  
Cell Recording ◽  
Channel Currents ◽  
Intracardiac Neurons

Cuevas, J. and Adams, D. J. M4 muscarinic receptor activation modulates calcium channel currents in rat intracardiac neurons. J. Neurophysiol. 78: 1903–1912, 1997. Modulation of high-voltage–activated Ca2+ channels by muscarinic receptor agonists was investigated in isolated parasympathetic neurons of neonatal rat intracardiac ganglia using the amphotericin B perforated-patch whole cell recording configuration of the patch-clamp technique. Focal application of the muscarinic agonists acetylcholine (ACh), muscarine, and oxotremorine-M to the voltage-clamped soma membrane reversibly depressed peak Ca2+ channel current amplitude. The dose-reponse relationship obtained for ACh-induced inhibition of Ba2+ current ( I Ba) exhibited a half-maximal inhibition at 6 nM. Maximal inhibition of I Ba amplitude obtained with 100 μM ACh was ∼75% compared with control at +10 mV. Muscarinic agonist-induced attenuation of Ca2+ channel currents was inhibited by the muscarinic receptor antagonists pirenzepine (≤300 nM) and m4-toxin (≤100 nM), but not by AF-DX 116 (300 nM) or m1-toxin (60 nM). The dose-response relationship obtained for antagonism of muscarine-induced inhibition of I Ba by m4-toxin gave an IC50 of 11 nM. These results suggest that muscarinic agonist-induced inhibition of high-voltage–activated Ca2+ channels in rat intracardiac neurons is mediated by the M4 muscarinic receptor. M4 receptor activation shifted the voltage dependence and depressed maximal activation of Ca2+ channels but had no effect on the steady-state inactivation of Ca2+ channels. Peak Ca2+ channel tail current amplitude was reduced ≥30% at +90 mV in the presence of ACh, indicating a voltage-independent component to the muscarinicreceptor-mediated inhibition. Both dihydropyridine- and ω-conotoxin GVIA–sensitive and -insensitive Ca2+ channels were inhibited by ACh, suggesting that the M4 muscarinic receptor is coupled to multiple Ca2+ channel subtypes in these neurons. Inhibition of I Ba amplitude by muscarinic agonists was also observed after cell dialysis using the conventional whole cell recording configuration. However, internal perfusion of the cell with 100 μM guanosine 5′-O-(2-thiodiphosphate) trilithium salt (GDP-β-S) or incubation of the neurons in Pertussis toxin (PTX) abolished the modulation of I Ba by muscarinic receptor agonists, suggesting the involvement of a PTX-sensitive G-protein in the signal transduction pathway. Given that ACh is the principal neurotransmitter mediating vagal innervation of the heart, the presence of this inhibitory mechanism in postganglionic intracardiac neurons suggests that it may serve for negative feedback regulation.

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