scholarly journals Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons

2016 ◽  
Vol 129 (22) ◽  
pp. 2714-2724 ◽  
Author(s):  
Jia-Qiang Zhang ◽  
Wan-Ying Xu ◽  
Chang-Qing Xu
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Inhibitory Synaptic Transmission

scholarly journals Mu-opioids suppress GABAergic synaptic transmission onto orbitofrontal cortex pyramidal neurons with subregional selectivity

2020 ◽  
Author(s):  
Benjamin K. Lau ◽  
Brittany P. Ambrose ◽  
Catherine S. Thomas ◽  
Min Qiao ◽  
Stephanie L. Borgland
Keyword(s):  
Synaptic Transmission ◽  
Opioid Receptor ◽  
Orbitofrontal Cortex ◽  
Pyramidal Neurons ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Inhibitory Synaptic Transmission ◽  
Receptor Coupling ◽  
Mu Opioids ◽  
Gabaergic Synaptic Transmission

AbstractThe orbitofrontal cortex (OFC) plays a critical role in evaluating outcomes in a changing environment. Administering opioids to the OFC can alter the hedonic reaction to food rewards and increase their consumption in a subregion specific manner. However, it is unknown how mu-opioid signalling influences synaptic transmission in the OFC. Thus, we investigated the cellular actions of mu-opioids within distinct subregions of the OFC. Using in-vitro patch clamp electrophysiology in brain slices containing the OFC, we found that the mu-opioid agonist, DAMGO produced a concentration-dependant inhibition of GABAergic synaptic transmission onto medial OFC (mOFC), but not lateral OFC (lOFC) neurons. This effect was mediated by presynaptic mu-opioid receptor activation of local parvalbumin (PV+)-expressing interneurons. The DAMGO-induced suppression of inhibition was long-lasting and not reversed upon washout of DAMGO, or by application of the mu-opioid receptor antagonist, CTAP, suggesting an inhibitory long-term depression (iLTD) induced by an exogenous mu-opioid. We show that LTD at inhibitory synapses is dependent on downstream cAMP/PKA signaling, which differs between the mOFC and lOFC. Finally, we demonstrate that endogenous opioid release triggered via moderate physiological stimulation can induce LTD. Taken together, these results suggest that presynaptic mu-opioid stimulation of local PV+ interneurons induces a long-lasting suppression of GABAergic synaptic transmission, which depends on subregional differences in mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascade. These findings provide mechanistic insight into the opposing functional effects produced by mu-opioids within the OFC.Significance StatementConsidering that both the OFC and the opioid system regulate reward, motivation, and food intake; understanding the role of opioid signaling within the OFC is fundamental for a mechanistic understanding of the sequelae for several psychiatric disorders. This study makes several novel observations. First, mu-opioids induce a long-lasting suppression of inhibitory synaptic transmission onto OFC pyramidal neurons in a regionally selective manner. Secondly, mu-opioids recruit PV+ inputs to suppress inhibitory synaptic transmission in the mOFC. Thirdly, the regional selectivity of mu-opioid action of endogenous opioids is due to the efficacy of mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascades. These experiments are the first to reveal a cellular mechanism of opioid action within the OFC.

scholarly journals Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus

2020 ◽  
Vol 295 (25) ◽  
pp. 8589-8595 ◽  
Author(s):  
Motokazu Uchigashima ◽  
Ming Leung ◽  
Takuya Watanabe ◽  
Amy Cheung ◽  
Timmy Le ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Single Cell ◽  
Pyramidal Neurons ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Dependent Manner ◽  
Splice Isoforms ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, trans-synaptic protein–protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry, and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that the NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform–dependent manner at hippocampal CA1 synapses. We also found that distinct subcellular localizations of the NLGN3 isoforms contribute to the functional differences observed among these isoforms. Finally, results from single-cell RNA-Seq analyses revealed that Nlgn1 and Nlgn3 are the major murine Nlgn genes and that the expression levels of the Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons. Our results delineate isoform-specific effects of Nlgn genes on the E-I balance in the murine hippocampus.

scholarly journals Age-dependent actions of dopamine on inhibitory synaptic transmission in superficial layers of mouse prefrontal cortex

2013 ◽  
Vol 109 (5) ◽  
pp. 1323-1332 ◽  
Author(s):  
Kush Paul ◽  
Charles L. Cox
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
D2 Receptor ◽  
Early Time ◽  
Inhibitory Response ◽  
Cellular Level ◽  
Inhibitory Synaptic Transmission ◽  
Time Period

Numerous developmental changes in the nervous system occur during the first several weeks of the rodent lifespan. Therefore, many characteristics of neuronal function described at the cellular level from in vitro slice experiments conducted during this early time period may not generalize to adult ages. We investigated the effect of dopamine (DA) on inhibitory synaptic transmission in superficial layers of the medial prefrontal cortex (PFC) in prepubertal [postnatal age (P; days) 12–20], periadolescent (P30–48), and adult (P70–100) mice. The PFC is associated with higher-level cognitive functions, such as working memory, and is associated with initiation, planning, and execution of actions, as well as motivation and cognition. It is innervated by DA-releasing fibers that arise from the ventral tegmental area. In slices from prepubertal mice, DA produced a biphasic modulation of inhibitory postsynaptic currents (IPSCs) recorded in layer II/ III pyramidal neurons. Activation of D2-like receptors leads to an early suppression of the evoked IPSC, which was followed by a longer-lasting facilitation of the IPSC mediated by D1-like DA receptors. In periadolescent mice, the D2 receptor-mediated early suppression was significantly smaller compared with the prepubertal animals and absent in adult animals. Furthermore, we found significant differences in the DA-mediated lasting enhancement of the inhibitory response among the developmental groups. Our findings suggest that behavioral paradigms that elicit dopaminergic release in the PFC differentially modulate inhibition of excitatory pyramidal neuron output in prepuberty compared with periadolescence and adulthood in the superficial layers (II/III) of the cortex.

scholarly journals Latrophilin-2 and latrophilin-3 are redundantly essential for parallel-fiber synapse function in cerebellum

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Roger Shen Zhang ◽  
Kif Liakath-Ali ◽  
Thomas C Südhof
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Pyramidal Neurons ◽  
Bergmann Glia ◽  
Parallel Fiber ◽  
Excitatory Synapses ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons ◽  
Double Deletion

Latrophilin-2 (Lphn2) and latrophilin-3 (Lphn3) are adhesion GPCRs that serve as postsynaptic recognition molecules in CA1 pyramidal neurons of the hippocampus, where they are localized to distinct dendritic domains and are essential for different sets of excitatory synapses. Here, we studied Lphn2 and Lphn3 in the cerebellum. We show that latrophilins are abundantly and differentially expressed in the cerebellar cortex. Using conditional KO mice, we demonstrate that the Lphn2/3 double-deletion but not the deletion of Lphn2 or Lphn3 alone suppresses parallel-fiber synapses and reduces parallel-fiber synaptic transmission by ~50% without altering release probability. Climbing-fiber synapses, conversely, were unaffected. Even though ~50% of total cerebellar Lphn3 protein is expressed in Bergmann glia, Lphn3 deletion from Bergmann glia did not detectably impair excitatory or inhibitory synaptic transmission. Our studies demonstrate that Lphn2 and Lphn3 are selectively but redundantly required in Purkinje cells for parallel-fiber synapses.

Mechanisms underlying rule learning-induced enhancement of excitatory and inhibitory synaptic transmission

2012 ◽  
Vol 107 (4) ◽  
pp. 1222-1229 ◽  
Author(s):  
Drorit Saar ◽  
Iris Reuveni ◽  
Edi Barkai
Keyword(s):  
Synaptic Transmission ◽  
Discrimination Learning ◽  
Ampa Receptor ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Piriform Cortex ◽  
Rule Learning ◽  
Olfactory Discrimination ◽  
Inhibitory Transmission ◽  
Inhibitory Synaptic Transmission

Training rats to perform rapidly and efficiently in an olfactory discrimination task results in robust enhancement of excitatory and inhibitory synaptic connectivity in the rat piriform cortex, which is maintained for days after training. To explore the mechanisms by which such synaptic enhancement occurs, we recorded spontaneous miniature excitatory and inhibitory synaptic events in identified piriform cortex neurons from odor-trained, pseudo-trained, and naive rats. We show that olfactory discrimination learning induces profound enhancement in the averaged amplitude of AMPA receptor-mediated miniature synaptic events in piriform cortex pyramidal neurons. Such physiological modifications are apparent at least 4 days after learning completion and outlast learning-induced modifications in the number of spines on these neurons. Also, the averaged amplitude of GABAA receptor-mediated miniature inhibitory synaptic events was significantly enhanced following odor discrimination training. For both excitatory and inhibitory transmission, an increase in miniature postsynaptic current amplitude was evident in most of the recorded neurons; however, some neurons showed an exceptionally great increase in the amplitude of miniature events. For both excitatory and inhibitory transmission, the frequency of spontaneous synaptic events was not modified after learning. These results suggest that olfactory discrimination learning-induced enhancement of synaptic transmission in cortical neurons is mediated by postsynaptic modulation of AMPA receptor-dependent currents and balanced by long-lasting modulation of postsynaptic GABAA receptor-mediated currents.

scholarly journals Hypoxia Results in GABAergic Channelopathy

2005 ◽  
Vol 5 (6) ◽  
pp. 234-235 ◽  
Author(s):  
Nicholas P. Poolos
Keyword(s):  
Synaptic Transmission ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Immature Brain ◽  
Fk 506 ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons ◽  
Developing Rat ◽  
In Vivo Administration

AMPA/Kainate Receptor–mediated Downregulation of GABAergic Synaptic Transmission by Calcineurin after Seizures in the Developing Rat Brain Sanchez RM, Dai W, Levada RE, Lippman JJ, Jensen FE J Neurosci 2005;25:3442–3451 Hypoxia is the most common cause of perinatal seizures and can be refractory to conventional anticonvulsant drugs, suggesting an age-specific form of epileptogenesis. A model of hypoxia-induced seizures in immature rats reveals that seizures result in immediate activation of the phosphatase calcineurin (CaN) in area CA1 of hippocampus. After seizures, CA1 pyramidal neurons exhibit a downregulation of GABAA receptor (GABAAR)-mediated inhibition that was reversed by CaN inhibitors. CaN activation appears to be dependent on seizure-induced activation of Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), because the upregulation of CaN activation and GABAAR inhibition were attenuated by GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] or Joro spider toxin. GABAAR β2/3 subunit protein was dephosphorylated at 1 h after seizures, suggesting this subunit as a possible substrate of CaN in this model. Finally, in vivo administration of the CaN inhibitor FK-506 significantly suppressed hypoxic seizures, and posttreatment with NBQX (2,3-dihydroxy-6-nitro-7-sulfonylbenzo[ f]quinoxaline) or FK-506 blocked the hypoxic seizure-induced increase in CaN expression. These data suggest that Ca2+-permeable AMPARs and CaN regulate inhibitory synaptic transmission in a novel plasticity pathway that may play a role in epileptogenesis in the immature brain.

scholarly journals Loss of microRNAs in pyramidal neurons leads to specific changes in inhibitory synaptic transmission in the prefrontal cortex

2012 ◽  
Vol 50 (3-4) ◽  
pp. 283-292 ◽  
Author(s):  
Ruby Hsu ◽  
Claude M. Schofield ◽  
Cassandra G. Dela Cruz ◽  
Dorothy M. Jones-Davis ◽  
Robert Blelloch ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Inhibitory Synaptic Transmission

scholarly journals Modulation of Inhibitory Synaptic Potentials in the Piriform Cortex

1999 ◽  
Vol 81 (5) ◽  
pp. 2103-2118 ◽  
Author(s):  
Madhvi M. Patil ◽  
Michael E. Hasselmo
Keyword(s):  
Synaptic Transmission ◽  
Associative Memory ◽  
Pyramidal Neurons ◽  
Piriform Cortex ◽  
Neuronal Firing ◽  
Physiological Data ◽  
Postsynaptic Potentials ◽  
Inhibitory Synaptic Transmission ◽  
Synaptic Potentials ◽  
Stimulation Of

Modulation of inhibitory synaptic potentials in the piriform cortex. Intracellular recordings from pyramidal neurons in brain slice preparations of the piriform cortex were used to test results from a computational model about the effects of cholinergic agonists on inhibitory synaptic potentials induced by stimulation of afferent fibers in layer Ia and association/intrinsic fibers in layer Ib. A simple model of piriform cortex as an associative memory was used to analyze how suppression of inhibitory synaptic transmission influenced performance of the network. Levels of suppression of excitatory synaptic transmission were set at levels determined in previous experimental work. Levels of suppression of inhibitory synaptic transmission were then systematically varied within the model. This modeling work demonstrated that suppression of inhibitory synaptic transmission in layer Ib should be stronger than suppression of inhibitory synaptic transmission in layer Ia to keep activity levels high enough for effective storage. Experimental data showed that perfusion of the cholinergic agonist carbachol caused a significant suppression of inhibitory postsynaptic potentials (IPSPs) in the pyramidal neurons that were induced by stimulation of layer Ib, with a weaker effect on IPSPs induced by stimulation of layer Ia. As previously described, carbachol also selectively suppressed excitatory postsynaptic potentials (EPSPs) elicited by intrinsic but not afferent fiber stimulation. The decrease in amplitude of IPSPs induced by layer Ib stimulation did not appear to be directly related to the decrease in EPSP amplitude induced by layer Ib stimulation. The stimulation necessary to induce neuronal firing with layer Ia stimulation was reduced in the presence of carbachol, whereas that necessary to induce neuronal firing with layer Ib stimulation was increased, despite the depolarization of resting membrane potential. Thus physiological data on cholinergic modulation of inhibitory synaptic potentials in the piriform cortex is compatible with the functional requirements determined from computational models of piriform cortex associative memory function.

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