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

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.

2009 ◽  
Vol 102 (2) ◽  
pp. 1049-1061 ◽  
Author(s):  
Sandra Westmark ◽  
Eugenio E. Oliveira ◽  
Joachim Schmidt

Stick insect middle leg (mesothoracic) motoneurons receive tonic excitatory input during front leg stepping on a treadmill. We studied the pharmacology of this excitatory input to the motoneurons during single-legged treadmill walking (in situ). During bath application of drugs restricted to the mesothoracic ganglion, activity in motoneurons contralateral to the stepping front leg was recorded from neuropilar processes. Application of the cholinergic antagonist atropine reduced the tonic depolarization amplitude. These results were compared with findings in acutely dissociated motoneuron cell bodies (in vitro) under whole cell voltage-clamp conditions. The presence of an acetylcholine-induced current in situ was supported by the finding of an acetylcholine evoked biphasic inward current with a sustained component that could be blocked by atropine. In situ the tonic depolarization was generally increased by application of the neuro-modulator octopamine and decreased by its antagonist mianserin. In vitro, however, octopamine reduced the inward current evoked by acetylcholine application to motoneurons. Intracellular application of bis-( o-aminophenoxy)- N,N,N',N'-tetraacetic acid (BAPTA) into motoneurons in situ revealed a dependence of the tonic depolarization on Ca2+ and application of the membrane-permeable cAMP analogue 8-bromo-cAMP increased the tonic depolarization. In contrast, 8-bromo-cAMP reduced the inward current evoked by acetylcholine application to motoneurons in vitro. We conclude that during walking, acetylcholine contributes to mediating the tonic depolarization possibly by acting on atropine-sensitive receptors on motoneurons. Octopamine that is released during walking increases the tonic depolarization. This increase, however, is not based on modulation of cholinergic action on motoneurons but rather on effects on premotor neurons. Both, Ca2+ and cAMP are likely second messengers involved in mediating the tonic depolarization, but whereas Ca2+ acts in motoneurons, cAMP does not appear to mediate a cholinergic depolarization in motoneurons.


2005 ◽  
Vol 93 (3) ◽  
pp. 1429-1438 ◽  
Author(s):  
Yong Lu ◽  
R. Michael Burger ◽  
Edwin W Rubel

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.


1996 ◽  
Vol 76 (2) ◽  
pp. 1166-1179 ◽  
Author(s):  
S. B. Kombian ◽  
J. A. Zidichouski ◽  
Q. J. Pittman

1. The effect of gamma-aminobutyric acid-B (GABAB)-receptor activation on excitatory synaptic transmission in the rat supraoptic nucleus (SON) was examined using the nystatin perforated-patch whole cell recording technique in coronal hypothalamic slices. 2. Stimulation of the hypothalamic region dorso-medial to the SON elicited glutamate and GABAA-receptor-mediated synaptic responses in electrophysiologically identified magnocellular neurosecretory cells. 3. Bath application of the GABAB-receptor agonist, +/- -baclofen reversibly reduced pharmacologically isolated, glutamate-mediated excitatory postsynaptic currents (EPSCs) in a concentration-dependent manner. At the concentrations used, baclofen altered neither the postsynaptic conductances of these cells nor their response to bath applied alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 4. The baclofen-induced synaptic depression was accompanied by an increase in paired pulse facilitation (PPF). This increase in PPF, as well as the synaptic depression, was blocked by the GABAB-receptor antagonists CGP36742 and saclofen. 5. In addition to blocking the actions of baclofen in this nucleus, CGP36742 caused an increase in the evoked EPSC amplitude without altering postsynaptic cell conductances or responses induced by bath-applied AMPA. Contrary to the action of CGP36742, saclofen caused a baclofen-like depression of the evoked EPSC, suggesting that it may act as a partial GABAB receptor agonist. 6. These results indicate that the activation of presynaptic GABAB receptors reduces fast excitatory synaptic transmission in the SON. They further suggest that presynaptic GABAB receptors may be tonically activated in vitro. Thus GABAB receptors may influence the level of activity and excitation of SON neurons and hence modulate the secretion of the regulatory neuropeptides vasopressin and oxytocin.


2020 ◽  
Vol 134 (3) ◽  
pp. 222-232
Author(s):  
Khulganaa Buyannemekh ◽  
Jessica B. Zito ◽  
Michelle L. Tomaszycki

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 34
Author(s):  
Mélody Dutot ◽  
Elodie Olivier ◽  
Sophie Fouyet ◽  
Romain Magny ◽  
Karim Hammad ◽  
...  

Phlorotannins are polyphenols occurring exclusively in some species of brown algae, known for numerous biological activities, e.g., antioxidant, antiproliferative, antidiabetic, and antiallergic properties. Their effects on the response of human lung cells to benzo[a]pyrene (B[a]P) has not been characterized. Our objective was to in vitro evaluate the effects of a phlorotannin-rich extract obtained from the brown algae Ascophyllum nodosum and Fucus vesiculosus on B[a]P cytotoxic effects. The A549 cell line was incubated with B[a]P for 48 and 72 h in the presence or absence of the brown algae extract. Cytochrome P450 activity, activation of P2X7 receptor, F-actin disorganization, and loss of E-cadherin expression were assessed using microplate cytometry and fluorescence microscopy. Relative to control, incubation with the brown algae extract was associated with lower B[a]P-induced CYP1 activity, lower P2X7 receptor activation, and lower reactive oxygen species production. The brown algae extract inhibited the alterations of F-actin arrangement and the downregulation of E-cadherin expression. We identified a phlorotannins-rich extract that could be deeper investigated as a cancer chemopreventive agent to block B[a]P-mediated carcinogenesis.


Life Sciences ◽  
2021 ◽  
Vol 278 ◽  
pp. 119541
Author(s):  
Aysegul Gorur ◽  
Miguel Patiño ◽  
Hideaki Takahashi ◽  
German Corrales ◽  
Curtis R. Pickering ◽  
...  

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