Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals

Lenkey, Nora; Kirizs, Tekla; Holderith, Noémi; Máté, Zoltán; Szabó, Gábor; Vizi, E. Sylvester; Hájos, Norbert; Nusser, Zoltán

doi:10.1038/ncomms7557

Cited by 41 publications

(34 citation statements)

References 51 publications

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“…Interestingly, although the rise time of the events originating from the CCKBCs was significantly slower, the location of their synapses was not distinct from those of PVBCs. This data indicates that the difference in rise times might derive from the spatiotemporal profile of neurotransmitter release, as it was described in the hippocampus (Bucurenciu et al, 2008; Lenkey et al, 2015). The distinct release machinery might also be responsible for the observed differences in the latency of the responses.…”

Section: Discussionsupporting

confidence: 66%

Perisomatic GABAergic synapses of basket cells effectively control principal neuron activity in amygdala networks

Veres

Nagy

Hájos

2017

eLife

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Efficient control of principal neuron firing by basket cells is critical for information processing in cortical microcircuits, however, the relative contribution of their perisomatic and dendritic synapses to spike inhibition is still unknown. Using in vitro electrophysiological paired recordings we reveal that in the mouse basal amygdala cholecystokinin- and parvalbumin-containing basket cells provide equally potent control of principal neuron spiking. We performed pharmacological manipulations, light and electron microscopic investigations to show that, although basket cells innervate the entire somato-denditic membrane surface of principal neurons, the spike controlling effect is achieved primarily via the minority of synapses targeting the perisomatic region. As the innervation patterns of individual basket cells on their different postsynaptic partners show high variability, the impact of inhibitory control accomplished by single basket cells is also variable. Our results show that both basket cell types can powerfully regulate the activity in amygdala networks predominantly via their perisomatic synapses.DOI: http://dx.doi.org/10.7554/eLife.20721.001

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Section: Discussionsupporting

confidence: 66%

Perisomatic GABAergic synapses of basket cells effectively control principal neuron activity in amygdala networks

Veres

Nagy

Hájos

2017

eLife

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“…Lenkey et al . () have tested the hypothesis that the strength of CB 1 ‐mediated modulation of GABA release is related to the CB 1 content of axon terminals. Using the CB 1 antagonist AM251 they have shown that it caused an increase in action potential‐evoked in GABA axons.…”

Section: Cannabinoids and Gabamentioning

confidence: 99%

Modulatory effects of cannabinoids on brain neurotransmission

Cohen

Weizman

Weinstein

2019

Eur J of Neuroscience

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Recreational and chronic cannabis use has been associated with a range of acute and chronic effects including; anti‐nociceptive actions, anxiety, depression, psychotic symptoms and neurocognitive impairments. The mechanisms underlying cannabinoid‐based drugs effects are not fully known but given the neuro‐modulatory functions of the endocannabinoid system, it seems likely that agonistic activity at the cannabinoid type‐1 receptors (CB1) might modulate the functions of other neurotransmitter systems. The present review has summarized the currently available pre‐clinical and clinical data on the interactions of CB1 and cannabinoid type‐2 receptors (CB2) with the central neurotransmitters; dopamine, serotonin, noradrenaline, GABA, glutamate and opioids. Acute and chronic exposures to cannabinoids exert pharmacological alterations in the mammalian brain that have profound implications for our understanding of the neuropharmacology of cannabinoid‐based drugs and their effects on mental health and the brain. A recent emergence uses of cannabis for medical purpose together with legalization and decriminalization of cannabis and increasing use of highly potent synthetic cannabinoids raise a growing concern over the effects of cannabinoids and their interaction with other neurotransmitters on physical and mental health.

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“…First we characterized the basic properties of inhibitory synaptic transmission between interneurons and their PC targets. We used a high KCl-based intrapipette solution for both pre-and postsynaptic cells (for details, see Methods) and used a CB 1 receptor antagonist AM251 to eliminate the potential tonic activation of CB 1 receptors at the output synapses of CCK+ cells, which might significantly alter the synaptic properties (Lenkey et al 2015). We calculated the basic properties of uIPSCs (10-90% rise time, decay time constant, latency, peak amplitude, synaptic potency and transmission probability) by averaging events evoked by single presynaptic spikes.…”

Section: The Type Of Interneuron Determines the Properties Of Uipscs mentioning

confidence: 99%

“…To pursue the molecular mechanism behind the differences of the release patterns is beyond the scope of the present study, although differences have been shown with respect to the Ca 2+ metabolism and release machinery for the two cell types (Hefft & Jonas, 2005;Lee et al 2009;Lenkey et al 2015).…”

Section: Differences In Transmission Properties (Unitary and Temporalmentioning

confidence: 99%

Properties and dynamics of inhibitory synaptic communication within the CA3 microcircuits of pyramidal cells and interneurons expressing parvalbumin or cholecystokinin

Kohus

Káli

Rovira-Esteban

et al. 2016

The Journal of Physiology

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Key pointsr To understand how a network operates, its elements must be identified and characterized, and the interactions of the elements need to be studied in detail.r In the present study, we describe quantitatively the connectivity of two classes of inhibitory neurons in the hippocampal CA3 area (parvalbumin-positive and cholecystokinin-positive interneurons), a key region for the generation of behaviourally relevant synchronous activity patterns.r We describe how interactions among these inhibitory cells and their local excitatory target neurons evolve over the course of physiological and pathological activity patterns.r The results of the present study enable the construction of precise neuronal network models that may help us understand how network dynamics is generated and how it can underlie information processing and pathological conditions in the brain.r We show how inhibitory dynamics between parvalbumin-positive basket cells and pyramidal cells could contribute to sharp wave-ripple generation.Abstract Different hippocampal activity patterns are determined primarily by the interaction of excitatory cells and different types of interneurons. To understand the mechanisms underlying the generation of different network dynamics, the properties of synaptic transmission need to be uncovered. Perisomatic inhibition is critical for the generation of sharp wave-ripples, gamma oscillations and pathological epileptic activities. Therefore, we aimed to quantitatively and systematically characterize the temporal properties of the synaptic transmission between perisomatic inhibitory neurons and pyramidal cells in the CA3 area of mouse hippocampal slices, using action potential patterns recorded during physiological and pathological network states. Parvalbumin-positive (PV+) and cholecystokinin-positive (CCK+) interneurons showed distinct intrinsic physiological features. Interneurons of the same type formed reciprocally connected subnetworks, whereas the connectivity between interneuron classes was sparse. The characteristics of unitary interactions depended on the identity of both synaptic partners, whereas the short-term plasticity of synaptic transmission depended mainly on the presynaptic cell type. PV+ interneurons showed frequency-dependent depression, whereas more complex dynamics characterized the output of CCK+ interneurons. We quantitatively captured the dynamics of transmission at these different types of connection with simple mathematical models, and describe in detail the response to physiological and pathological discharge patterns. Our data suggest that the temporal propeties of PV+ interneuron transmission may contribute to sharp wave-ripple generation.

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Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals

Cited by 41 publications

References 51 publications

Perisomatic GABAergic synapses of basket cells effectively control principal neuron activity in amygdala networks

Perisomatic GABAergic synapses of basket cells effectively control principal neuron activity in amygdala networks

Modulatory effects of cannabinoids on brain neurotransmission

Properties and dynamics of inhibitory synaptic communication within the CA3 microcircuits of pyramidal cells and interneurons expressing parvalbumin or cholecystokinin

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