Differential effects of the group II mGluR agonist, DCG-IV, on depolarization-induced suppression of inhibition in hippocampal CA1 and CA3 neurons

Morishita, Wade; Alger, Bradley E.

doi:10.1002/1098-1063(2000)10:3<261::aid-hipo6>3.0.co;2-1

Cited by 19 publications

(3 citation statements)

References 30 publications

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“…There is a notable expression of CB1Rs in the basal ganglia, mainly in the Striatum, GP, EP, and SNr (Herkenham et al, 1990). Activation of the CB1R modulates LTD and also short-term plasticity (Llano et al, 1991;Pitler and Alger, 1992;Morishita and Alger, 2000;Kreitzer and Regehr, 2001;Ohno-Shosaku et al, 2001;Wilson and Nicoll, 2001). This modulation of short-term plasticity appears in several basal ganglia regions including the striatum (Kreitzer and Malenka, 2005;Freiman et al, 2006;Narushima et al, 2006aNarushima et al, ,b, 2007Yin and Lovinger, 2006;Centonze et al, 2007;Uchigashima et al, 2007;Maccarrone et al, 2008), GP (Engler, 2005), SNr (Yanovsky et al, 2003;Engler, 2005;Szabo et al, 2006), SNc (Szabo et al, 2006), and NAc (Rancz and Ha, 2006).…”

Section: Discussionmentioning

confidence: 98%

Endocannabinoids and Dopamine Balance Basal Ganglia Output

Gorodetski

Loewenstern

Faynveitz

et al. 2021

Front. Cell. Neurosci.

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The entopeduncular nucleus is one of the basal ganglia's output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the Striatum and the globus pallidus, together with glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all these primary afferents to the entopeduncular nucleus. Our results suggest that the interplay between dopamine and endocannabinoids determines the balance between direct pathway (striatum) and indirect pathway (globus pallidus) in entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoid diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.

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Section: Discussionmentioning

confidence: 98%

Endocannabinoids and Dopamine Balance Basal Ganglia Output

Gorodetski

Loewenstern

Faynveitz

et al. 2021

Front. Cell. Neurosci.

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“…Responses to KCl depolarization, TBOA inhibition of glutamate reuptake, the 5-HT 6 antagonist SB-399885 (3 μM ± 120 mM KCl), group III mGlu antagonist CPPG (100 μM ± 120 mM KCl), and mGlu 7 allosteric antagonist MMPIP (100 μM ± 120 mM KCl) were then compared in slices from the four different neurodevelopmental conditions (PND 73-112). Antagonist concentrations were similar to previous in vitro [51,52] and hippocampal slice [53,54] studies, and intentionally higher than achieved in vivo to allow for slice penetration [55]. Compounds (one per slice) were perfused via the aCSF reservoir (10 min or 15 min for 5-HT 6 / mGlu antagonists with high KCl) or applied direct to slices (αlatrotoxin).…”

Section: Glutamate Microsensor Recordingsmentioning

confidence: 99%

Calbindin Deficits May Underlie Dissociable Effects of 5-HT6 and mGlu7 Antagonists on Glutamate and Cognition in a Dual-Hit Neurodevelopmental Model for Schizophrenia

et al. 2020

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Despite several compounds entering clinical trials for the negative and cognitive symptoms of schizophrenia, few have progressed beyond phase III. This is partly attributed to a need for improved preclinical models, to understand disease and enable predictive evaluation of novel therapeutics. To this end, one recent approach incorporates "dual-hit" neurodevelopmental insults like neonatal phencyclidine plus isolation rearing (PCP-Iso). Glutamatergic dysfunction contributes to schizophrenia pathophysiology and may represent a treatment target, so we used enzyme-based microsensors to evaluate basal-and drugevoked glutamate release in hippocampal slices from rats that received neonatal PCP and/or isolation rearing. 5-HT 6 antagonistevoked glutamate release (thought to be mediated indirectly via GABAergic disinhibition) was reduced in PCP-Iso, as were cognitive effects of a 5-HT 6 antagonist in a hippocampal glutamate-dependent novel object discrimination task. Yet mGlu 7 antagonist-evoked glutamatergic and cognitive responses were spared. Immunohistochemical analyses suggest these findings (which mirror the apparent lack of clinical response to 5-HT 6 antagonists in schizophrenia) are not due to reduced hippocampal 5-HT input in PCP-Iso, but may be explained by reduced calbindin expression. This calcium-binding protein is present in a subset of GABAergic interneurons receiving preferential 5-HT innervation and expressing 5-HT 6 receptors. Its loss (in schizophrenia and PCP-Iso) would be expected to reduce interneuron firing and potentially prevent further 5-HT 6 antagonist-mediated disinhibition, without impacting on responses of VIP-expressing interneurons to mGlu 7 antagonism. This research highlights the importance of improved understanding for selection of appropriate preclinical models, especially where disease neurobiology impacts on cells mediating the effects of potential therapeutics.

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“…This suggests that a chemical messenger generated during depolarization of the pyramidal neurons must travel backwards across the synapse to induce DSI. DSI has been observed in both excitatory and inhibitory neurons in hippocampal cell culture [217], in CA3 pyramidal cells [203], in den- tate gyrus granule cells [4], and in neocortical pyramidal cells [320].…”

Section: Regulation Of Short-term Synaptic Plasticitymentioning

confidence: 99%

Neuropharmacology of the Endocannabinoid Signaling System-Molecular Mechanisms, Biological Actions and Synaptic Plasticity

Basavarajappa¹

2007

103

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The endocannabinoid signaling system is composed of the cannabinoid receptors; their endogenous ligands, the endocannabinoids; the enzymes that produce and inactivate the endocannabinoids; and the endocannabinoid transporters. The endocannabinoids are a new family of lipidic signal mediators, which includes amides, esters, and ethers of long-chain polyunsaturated fatty acids. Endocannabinoids signal through the same cell surface receptors that are targeted by Delta(9)-tetrahydrocannabinol (Delta(9)THC), the active principles of cannabis sativa preparations like hashish and marijuana. The biosynthetic pathways for the synthesis and release of endocannabinoids are still rather uncertain. Unlike neurotransmitter molecules that are typically held in vesicles before synaptic release, endocannabinoids are synthesized on demand within the plasma membrane. Once released, they travel in a retrograde direction and transiently suppress presynaptic neurotransmitter release through activation of cannabinoid receptors. The endocannabinoid signaling system is being found to be involved in an increasing number of pathological conditions. In the brain, endocannabinoid signaling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in central nervous system (CNS) disease. Their ability to modulate synaptic efficacy has a wide range of functional consequences and provides unique therapeutic possibilities. The present review is focused on new information regarding the endocannabinoid signaling system in the brain. First, the structure, anatomical distribution, and signal transduction mechanisms of cannabinoid receptors are described. Second, the synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation. Finally, the role of the endocannabinoid signaling system in the CNS and its potential as a therapeutic target in various CNS disease conditions, including alcoholism, are discussed.

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Differential effects of the group II mGluR agonist, DCG-IV, on depolarization-induced suppression of inhibition in hippocampal CA1 and CA3 neurons

Cited by 19 publications

References 30 publications

Endocannabinoids and Dopamine Balance Basal Ganglia Output

Endocannabinoids and Dopamine Balance Basal Ganglia Output

Calbindin Deficits May Underlie Dissociable Effects of 5-HT6 and mGlu7 Antagonists on Glutamate and Cognition in a Dual-Hit Neurodevelopmental Model for Schizophrenia

Neuropharmacology of the Endocannabinoid Signaling System-Molecular Mechanisms, Biological Actions and Synaptic Plasticity

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