 |
 Previous Article | Next Article 
The Journal of Neuroscience, June 1, 1999, 19(11):4544-4558
Presynaptically Located CB1 Cannabinoid Receptors Regulate GABA
Release from Axon Terminals of Specific Hippocampal
Interneurons
István
Katona1,
Beáta
Sperlágh1,
Attila
Sík1,
Attila
Käfalvi1,
E. Sylvester
Vizi1,
Ken
Mackie2, and
Tamás F.
Freund1
1 Institute of Experimental Medicine, Hungarian Academy
of Sciences, Budapest, H-1450, Hungary, and 2 Departments
of Anesthesiology, and Physiology and Biophysics, University of
Washington, Seattle, Washington 98195
To understand the functional significance and mechanisms of action
in the CNS of endogenous and exogenous cannabinoids, it is crucial to
identify the neural elements that serve as the structural substrate of
these actions. We used a recently developed antibody against the CB1
cannabinoid receptor to study this question in hippocampal networks.
Interneurons with features typical of basket cells showed a selective,
intense staining for CB1 in all hippocampal subfields and layers. Most
of them (85.6%) contained cholecystokinin (CCK), which corresponded to
96.9% of all CCK-positive interneurons, whereas only 4.6% of the
parvalbumin (PV)-containing basket cells expressed CB1. Accordingly,
electron microscopy revealed that CB1-immunoreactive axon terminals of
CCK-containing basket cells surrounded the somata and proximal
dendrites of pyramidal neurons, whereas PV-positive basket cell
terminals in similar locations were negative for CB1. The synthetic
cannabinoid agonist WIN 55,212-2 (0.01-3 µM) reduced
dose-dependently the electrical field stimulation-induced [3H]GABA release from superfused hippocampal
slices, with an EC50 value of 0.041 µM.
Inhibition of GABA release by WIN 55,212-2 was not mediated by
inhibition of glutamatergic transmission because the WIN 55,212-2 effect was not reduced by the glutamate blockers AP5 and CNQX. In
contrast, the CB1 cannabinoid receptor antagonist SR 141716A (1 µM) prevented this effect, whereas by itself it did not
change the outflow of [3H]GABA.
These results suggest that cannabinoid-mediated modulation of
hippocampal interneuron networks operate largely via presynaptic receptors on CCK-immunoreactive basket cell terminals. Reduction of
GABA release from these terminals is the likely mechanism by which both
endogenous and exogenous CB1 ligands interfere with hippocampal network
oscillations and associated cognitive functions.
Key words:
interneurons; cannabinoids; GABA; inhibition; cholecystokinin; parvalbumin; hippocampus, anxiety
Copyright © 1999 Society for Neuroscience 0270-6474/99/19114544-15$05.00/0
This article has been cited by other articles:
|
|
|
|
 
A. Sheinin, G. Talani, M. I. Davis, and D. M. Lovinger
Endocannabinoid- and mGluR5-Dependent Short-Term Synaptic Depression in an Isolated Neuron/Bouton Preparation From the Hippocampal CA1 Region
J Neurophysiol,
August 1, 2008;
100(2):
1041 - 1052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Klausberger and P. Somogyi
Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations
Science,
July 4, 2008;
321(5885):
53 - 57.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Edwards, L. Zhang, and B. E. Alger
Metaplastic control of the endocannabinoid system at inhibitory synapses in hippocampus
PNAS,
June 10, 2008;
105(23):
8142 - 8147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Kim, J. J. Waataja, and S. A. Thayer
Cannabinoids Inhibit Network-Driven Synapse Loss between Hippocampal Neurons in Culture
J. Pharmacol. Exp. Ther.,
June 1, 2008;
325(3):
850 - 858.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Sjostrom, E. A. Rancz, A. Roth, and M. Hausser
Dendritic Excitability and Synaptic Plasticity
Physiol Rev,
April 1, 2008;
88(2):
769 - 840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ludanyi, L. Eross, S. Czirjak, J. Vajda, P. Halasz, M. Watanabe, M. Palkovits, Z. Magloczky, T. F. Freund, and I. Katona
Downregulation of the CB1 Cannabinoid Receptor and Related Molecular Elements of the Endocannabinoid System in Epileptic Human Hippocampus
J. Neurosci.,
March 19, 2008;
28(12):
2976 - 2990.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. L. Glickfeld, B. V. Atallah, and M. Scanziani
Complementary Modulation of Somatic Inhibition by Opioids and Cannabinoids
J. Neurosci.,
February 20, 2008;
28(8):
1824 - 1832.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Pan, C. J. Hillard, and Q.-s. Liu
Endocannabinoid Signaling Mediates Cocaine-Induced Inhibitory Synaptic Plasticity in Midbrain Dopamine Neurons
J. Neurosci.,
February 6, 2008;
28(6):
1385 - 1397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ben-Ari, J.-L. Gaiarsa, R. Tyzio, and R. Khazipov
GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations
Physiol Rev,
October 1, 2007;
87(4):
1215 - 1284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. K. Makara, I. Katona, G. Nyiri, B. Nemeth, C. Ledent, M. Watanabe, J. de Vente, T. F. Freund, and N. Hajos
Involvement of Nitric Oxide in Depolarization-Induced Suppression of Inhibition in Hippocampal Pyramidal Cells during Activation of Cholinergic Receptors
J. Neurosci.,
September 19, 2007;
27(38):
10211 - 10222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-H. Kang-Park, W. A. Wilson, C. M. Kuhn, S. D. Moore, and H. S. Swartzwelder
Differential Sensitivity of GABAA Receptor-Mediated IPSCs to Cannabinoids in Hippocampal Slices From Adolescent and Adult Rats
J Neurophysiol,
September 1, 2007;
98(3):
1223 - 1230.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Carter and X.-J. Wang
Cannabinoid-Mediated Disinhibition and Working Memory: Dynamical Interplay of Multiple Feedback Mechanisms in a Continuous Attractor Model of Prefrontal Cortex
Cereb Cortex,
September 1, 2007;
17(suppl_1):
i16 - i26.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Ali
Presynaptic Inhibition of GABAA Receptor-Mediated Unitary IPSPs by Cannabinoid Receptors at Synapses Between CCK-Positive Interneurons in Rat Hippocampus
J Neurophysiol,
August 1, 2007;
98(2):
861 - 869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Tukker, P. Fuentealba, K. Hartwich, P. Somogyi, and T. Klausberger
Cell Type-Specific Tuning of Hippocampal Interneuron Firing during Gamma Oscillations In Vivo
J. Neurosci.,
August 1, 2007;
27(31):
8184 - 8189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Szabadits, C. Cserep, A. Ludanyi, I. Katona, J. Gracia-Llanes, T. F. Freund, and G. Nyiri
Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling
J. Neurosci.,
July 25, 2007;
27(30):
8101 - 8111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Zhu and D. M. Lovinger
Persistent Synaptic Activity Produces Long-Lasting Enhancement of Endocannabinoid Modulation and Alters Long-Term Synaptic Plasticity
J Neurophysiol,
June 1, 2007;
97(6):
4386 - 4389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Huang, C. Acuna-Goycolea, Y. Li, H. M. Cheng, K. Obrietan, and A. N. van den Pol
Cannabinoids Excite Hypothalamic Melanin-Concentrating Hormone But Inhibit Hypocretin/Orexin Neurons: Implications for Cannabinoid Actions on Food Intake and Cognitive Arousal
J. Neurosci.,
May 2, 2007;
27(18):
4870 - 4881.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Uchigashima, M. Narushima, M. Fukaya, I. Katona, M. Kano, and M. Watanabe
Subcellular Arrangement of Molecules for 2-Arachidonoyl-Glycerol-Mediated Retrograde Signaling and Its Physiological Contribution to Synaptic Modulation in the Striatum
J. Neurosci.,
April 4, 2007;
27(14):
3663 - 3676.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Hashimotodani, T. Ohno-Shosaku, and M. Kano
Endocannabinoids and Synaptic Function in the CNS
Neuroscientist,
April 1, 2007;
13(2):
127 - 137.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. L. Hill, T. Gallopin, I. Ferezou, B. Cauli, J. Rossier, P. Schweitzer, and B. Lambolez
Functional CB1 Receptors Are Broadly Expressed in Neocortical GABAergic and Glutamatergic Neurons
J Neurophysiol,
April 1, 2007;
97(4):
2580 - 2589.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Alle and J. R. P. Geiger
GABAergic Spill-Over Transmission onto Hippocampal Mossy Fiber Boutons
J. Neurosci.,
January 24, 2007;
27(4):
942 - 950.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Chen, A. Neu, A. L. Howard, C. Foldy, J. Echegoyen, L. Hilgenberg, M. Smith, K. Mackie, and I. Soltesz
Prevention of Plasticity of Endocannabinoid Signaling Inhibits Persistent Limbic Hyperexcitability Caused by Developmental Seizures
J. Neurosci.,
January 3, 2007;
27(1):
46 - 58.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Fortin and E. S. Levine
Differential Effects of Endocannabinoids on Glutamatergic and GABAergic Inputs to Layer 5 Pyramidal Neurons
Cereb Cortex,
January 1, 2007;
17(1):
163 - 174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Eggan and D. A. Lewis
Immunocytochemical Distribution of the Cannabinoid CB1 Receptor in the Primate Neocortex: A Regional and Laminar Analysis
Cereb Cortex,
January 1, 2007;
17(1):
175 - 191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Neu, C. Foldy, and I. Soltesz
Postsynaptic origin of CB1-dependent tonic inhibition of GABA release at cholecystokinin-positive basket cell to pyramidal cell synapses in the CA1 region of the rat hippocampus
J. Physiol.,
January 1, 2007;
578(1):
233 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. F. Hoffman, M. Oz, R. Yang, A. H. Lichtman, and C. R. Lupica
Opposing actions of chronic {Delta}9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation
Learn. Mem.,
January 1, 2007;
14(1-2):
63 - 74.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Biro, N. B. Holderith, and Z. Nusser
Release Probability-Dependent Scaling of the Postsynaptic Responses at Single Hippocampal GABAergic Synapses
J. Neurosci.,
November 29, 2006;
26(48):
12487 - 12496.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Hofmann, B. Nahir, and C. J. Frazier
Endocannabinoid-Mediated Depolarization-Induced Suppression of Inhibition in Hilar Mossy Cells of the Rat Dentate Gyrus
J Neurophysiol,
November 1, 2006;
96(5):
2501 - 2512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. D. Skosnik, G. P. Krishnan, E. E. Aydt, H. A. Kuhlenshmidt, and B. F. O'Donnell
Psychophysiological Evidence of Altered Neural Synchronization in Cannabis Use: Relationship to Schizotypy
Am J Psychiatry,
October 1, 2006;
163(10):
1798 - 1805.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Pacher, S. Batkai, and G. Kunos
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pharmacol. Rev.,
September 1, 2006;
58(3):
389 - 462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Katona, G. M. Urban, M. Wallace, C. Ledent, K.-M. Jung, D. Piomelli, K. Mackie, and T. F. Freund
Molecular Composition of the Endocannabinoid System at Glutamatergic Synapses
J. Neurosci.,
May 24, 2006;
26(21):
5628 - 5637.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Domenici, S. C. Azad, G. Marsicano, A. Schierloh, C. T. Wotjak, H.-U. Dodt, W. Zieglgansberger, B. Lutz, and G. Rammes
Cannabinoid Receptor Type 1 Located on Presynaptic Terminals of Principal Neurons in the Forebrain Controls Glutamatergic Synaptic Transmission
J. Neurosci.,
May 24, 2006;
26(21):
5794 - 5799.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yoshida, M. Fukaya, M. Uchigashima, E. Miura, H. Kamiya, M. Kano, and M. Watanabe
Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor.
J. Neurosci.,
May 3, 2006;
26(18):
4740 - 4751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Leterrier, J. Laine, M. Darmon, H. Boudin, J. Rossier, and Z. Lenkei
Constitutive activation drives compartment-selective endocytosis and axonal targeting of type 1 cannabinoid receptors.
J. Neurosci.,
March 22, 2006;
26(12):
3141 - 3153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kawamura, M. Fukaya, T. Maejima, T. Yoshida, E. Miura, M. Watanabe, T. Ohno-Shosaku, and M. Kano
The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum.
J. Neurosci.,
March 15, 2006;
26(11):
2991 - 3001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Pagotto, G. Marsicano, D. Cota, B. Lutz, and R. Pasquali
The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance
Endocr. Rev.,
February 1, 2006;
27(1):
73 - 100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Foldy, A. Neu, M. V. Jones, and I. Soltesz
Presynaptic, Activity-Dependent Modulation of Cannabinoid Type 1 Receptor-Mediated Inhibition of GABA Release
J. Neurosci.,
February 1, 2006;
26(5):
1465 - 1469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Berghuis, M. B. Dobszay, X. Wang, S. Spano, F. Ledda, K. M. Sousa, G. Schulte, P. Ernfors, K. Mackie, G. Paratcha, et al.
Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor
PNAS,
December 27, 2005;
102(52):
19115 - 19120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Klausberger, L. F. Marton, J. O'Neill, J. H. J. Huck, Y. Dalezios, P. Fuentealba, W. Y. Suen, E. Papp, T. Kaneko, M. Watanabe, et al.
Complementary Roles of Cholecystokinin- and Parvalbumin-Expressing GABAergic Neurons in Hippocampal Network Oscillations
J. Neurosci.,
October 19, 2005;
25(42):
9782 - 9793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zilberter, T. Harkany, and C. D. Holmgren
Dendritic Release of Retrograde Messengers Controls Synaptic Transmission in Local Neocortical Networks
Neuroscientist,
August 1, 2005;
11(4):
334 - 344.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. L. Bodor, I. Katona, G. Nyiri, K. Mackie, C. Ledent, N. Hajos, and T. F. Freund
Endocannabinoid Signaling in Rat Somatosensory Cortex: Laminar Differences and Involvement of Specific Interneuron Types
J. Neurosci.,
July 20, 2005;
25(29):
6845 - 6856.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bernard, M. Milh, Y. M. Morozov, Y. Ben-Ari, T. F. Freund, and H. Gozlan
Altering cannabinoid signaling during development disrupts neuronal activity
PNAS,
June 28, 2005;
102(26):
9388 - 9393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kofalvi, R. J. Rodrigues, C. Ledent, K. Mackie, E. S. Vizi, R. A. Cunha, and B. Sperlagh
Involvement of Cannabinoid Receptors in the Regulation of Neurotransmitter Release in the Rodent Striatum: A Combined Immunochemical and Pharmacological Analysis
J. Neurosci.,
March 16, 2005;
25(11):
2874 - 2884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Somogyi and T. Klausberger
Defined types of cortical interneurone structure space and spike timing in the hippocampus
J. Physiol.,
January 1, 2005;
562(1):
9 - 26.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Foldy, J. Dyhrfjeld-Johnsen, and I. Soltesz
Structure of cortical microcircuit theory
J. Physiol.,
January 1, 2005;
562(1):
47 - 54.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Galarreta, F. Erdelyi, G. Szabo, and S. Hestrin
Electrical Coupling among Irregular-Spiking GABAergic Interneurons Expressing Cannabinoid Receptors
J. Neurosci.,
November 3, 2004;
24(44):
9770 - 9778.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Fortin, J. Trettel, and E. S. Levine
Brief Trains of Action Potentials Enhance Pyramidal Neuron Excitability Via Endocannabinoid-Mediated Suppression of Inhibition
J Neurophysiol,
October 1, 2004;
92(4):
2105 - 2112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. V. Derbenev, T. C. Stuart, and B. N. Smith
Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve
J. Physiol.,
September 15, 2004;
559(3):
923 - 938.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Rusakov, A. Wuerz, and D. M. Kullmann
Heterogeneity and Specificity of Presynaptic Ca2+ Current Modulation by mGluRs at Individual Hippocampal Synapses
Cereb Cortex,
July 1, 2004;
14(7):
748 - 758.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. P. Brown, P. K. Safo, and W. G. Regehr
Endocannabinoids Inhibit Transmission at Granule Cell to Purkinje Cell Synapses by Modulating Three Types of Presynaptic Calcium Channels
J. Neurosci.,
June 16, 2004;
24(24):
5623 - 5631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Harkany, C. Holmgren, W. Hartig, T. Qureshi, F. A. Chaudhry, J. Storm-Mathisen, M. B. Dobszay, P. Berghuis, G. Schulte, K. M. Sousa, et al.
Endocannabinoid-Independent Retrograde Signaling at Inhibitory Synapses in Layer 2/3 of Neocortex: Involvement of Vesicular Glutamate Transporter 3
J. Neurosci.,
May 26, 2004;
24(21):
4978 - 4988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Galante and M. A. Diana
Group I Metabotropic Glutamate Receptors Inhibit GABA Release at Interneuron-Purkinje Cell Synapses through Endocannabinoid Production
J. Neurosci.,
May 19, 2004;
24(20):
4865 - 4874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Trettel, D. A. Fortin, and E. S. Levine
Endocannabinoid signalling selectively targets perisomatic inhibitory inputs to pyramidal neurones in juvenile mouse neocortex
J. Physiol.,
April 1, 2004;
556(1):
95 - 107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Losonczy, A. A. Biro, and Z. Nusser
Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons
PNAS,
February 3, 2004;
101(5):
1362 - 1367.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. G. Bazan
Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor
J. Lipid Res.,
December 1, 2003;
44(12):
2221 - 2233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Yao, P. Fan, Z. Jiang, W. S. Mailliard, A. S. Gordon, and I. Diamond
Addicting drugs utilize a synergistic molecular mechanism in common requiring adenosine and Gi-{beta}{gamma} dimers
PNAS,
November 25, 2003;
100(24):
14379 - 14384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Marsicano, S. Goodenough, K. Monory, H. Hermann, M. Eder, A. Cannich, S. C. Azad, M. G. Cascio, S. O. Gutierrez, M. van der Stelt, et al.
CB1 Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity
Science,
October 3, 2003;
302(5642):
84 - 88.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
