Tags

Type your tag names separated by a space and hit enter

Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons.
Neuroscience 2012; 201:46-56N

Abstract

Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin neurons by activation of presynaptic adenosine A1 receptors, which may finely regulate the excitability of these neurons as well as eventually modulate the sleep-wakefulness.

Authors+Show Affiliations

Department of Physiology, Third Military Medical University, 30 Gaotanyan Street, Chongqing, 400038, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22119641

Citation

Xia, J X., et al. "Presynaptic Inhibition of GABAergic Synaptic Transmission By Adenosine in Mouse Hypothalamic Hypocretin Neurons." Neuroscience, vol. 201, 2012, pp. 46-56.
Xia JX, Xiong JX, Wang HK, et al. Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons. Neuroscience. 2012;201:46-56.
Xia, J. X., Xiong, J. X., Wang, H. K., Duan, S. M., Ye, J. N., & Hu, Z. A. (2012). Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons. Neuroscience, 201, pp. 46-56. doi:10.1016/j.neuroscience.2011.11.019.
Xia JX, et al. Presynaptic Inhibition of GABAergic Synaptic Transmission By Adenosine in Mouse Hypothalamic Hypocretin Neurons. Neuroscience. 2012 Jan 10;201:46-56. PubMed PMID: 22119641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons. AU - Xia,J X, AU - Xiong,J X, AU - Wang,H K, AU - Duan,S M, AU - Ye,J N, AU - Hu,Z A, Y1 - 2011/11/17/ PY - 2011/08/10/received PY - 2011/11/08/revised PY - 2011/11/08/accepted PY - 2011/11/29/entrez PY - 2011/11/29/pubmed PY - 2012/5/15/medline SP - 46 EP - 56 JF - Neuroscience JO - Neuroscience VL - 201 N2 - Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin neurons by activation of presynaptic adenosine A1 receptors, which may finely regulate the excitability of these neurons as well as eventually modulate the sleep-wakefulness. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/22119641/Presynaptic_inhibition_of_GABAergic_synaptic_transmission_by_adenosine_in_mouse_hypothalamic_hypocretin_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(11)01286-3 DB - PRIME DP - Unbound Medicine ER -