Serotoninergic modulation of GABAergic synaptic transmission in developing rat CA3 pyramidal neurons

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.

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Dopamine D2 receptors modulate intrinsic properties and synaptic transmission of parvalbumin interneurons in the mouse primary motor cortex

10.1101/802140 ◽

2019 ◽

Author(s):

Jérémy Cousineau ◽

Léa Lescouzères ◽

Anne Taupignon ◽

Lorena Delgado-Zabalza ◽

Emmanuel Valjent ◽

...

Keyword(s):

Motor Cortex ◽

Synaptic Transmission ◽

Motor Skills ◽

Primary Motor Cortex ◽

Pyramidal Neurons ◽

D2 Receptors ◽

Receptor Subtypes ◽

Parvalbumin Interneurons ◽

Layer V ◽

Gabaergic Synaptic Transmission

AbstractDopamine (DA) plays a crucial role in the control of motor and higher cognitive functions such as learning, working memory and decision making. The primary motor cortex (M1), which is essential for motor control and the acquisition of motor skills, receives dopaminergic inputs in its superficial and deep layers from the midbrain. However, the precise action of DA and DA receptor subtypes on the cortical microcircuits of M1 remains poorly understood. The aim of this work was to investigate how DA, through the activation of D2 receptors (D2R), modulates the cellular and synaptic activity of M1 parvalbumin-expressing interneurons (PVINs) which are crucial to regulate the spike output of pyramidal neurons (PNs). By combining immunofluorescence, ex vivo electrophysiology, pharmacology and optogenetics approaches, we show that D2R activation increases neuronal excitability of PVINs and GABAergic synaptic transmission between PVINs and PNs in layer V of M1. Our data reveal a mechanism through which cortical DA modulates M1 microcircuitry and might participate in the acquisition of motor skills.Significance StatementPrimary motor cortex (M1), which is a region essential for motor control and the acquisition of motor skills, receives dopaminergic inputs from the midbrain. However, precise action of dopamine and its receptor subtypes on specific cell types in M1 remained poorly understood. Here, we demonstrate in M1 that dopamine D2 receptors (D2R) are present in parvalbumin interneurons (PVINs) and their activation increases the excitability of the PVINs, which are crucial to regulate the spike output of pyramidal neurons (PNs). Moreover the activation of the D2R facilitates the GABAergic synaptic transmission of those PVINs on layer V PNs. These results highlight how cortical dopamine modulates the functioning of M1 microcircuit which activity is disturbed in hypo- and hyperdopaminergic states.

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Levetiracetam (ucb LO59) affects in vitro models of epilepsy in CA3 pyramidal neurons without altering normal synaptic transmission

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/pl00005097 ◽

1997 ◽

Vol 356 (5) ◽

pp. 611-618 ◽

Cited By ~ 66

Author(s):

Susanne Birnstiel ◽

Ernst Wülfert ◽

S. G. Beck

Keyword(s):

Synaptic Transmission ◽

Pyramidal Neurons ◽

In Vitro Models ◽

Ca3 Pyramidal Neurons ◽

Models Of Epilepsy

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Cordycepin suppresses glutamatergic and GABAergic synaptic transmission through activation of A1 adenosine receptor in rat hippocampal CA1 pyramidal neurons

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.112446 ◽

2022 ◽

Vol 145 ◽

pp. 112446

Author(s):

Jinxiu Wang ◽

Yanchun Gong ◽

Haoyuan Tan ◽

Wenxi Li ◽

Baiyi Yan ◽

...

Keyword(s):

Synaptic Transmission ◽

Adenosine Receptor ◽

Pyramidal Neurons ◽

A1 Adenosine Receptor ◽

Ca1 Pyramidal Neurons ◽

Hippocampal Ca1 ◽

Gabaergic Synaptic Transmission

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Hypoxia Results in GABAergic Channelopathy

Epilepsy Currents ◽

10.1111/j.1535-7511.2005.00073.x ◽

2005 ◽

Vol 5 (6) ◽

pp. 234-235 ◽

Cited By ~ 1

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.

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