title: Endocannabinoid signaling in rat somatosensory cortex: laminar differences and involvement of specific interneuron types.
abstract: Endocannabinoid-mediated retrograde signaling exerts powerful control over synaptic transmission in many brain areas. However, in the neocortex, the precise laminar, cellular, and subcellular localization of the type 1 cannabinoid receptor (CB1) as well as its function has been elusive. Here we combined multiple immunolabeling with whole-cell recordings to investigate the morpho-functional characteristics of cannabinoid signaling in rat somatosensory cortex. Immunostaining for CB1 revealed axonal and somatic labeling with striking layer specificity: a high density of CB1-positive fibers was seen in layers II-III, in layer VI, and in upper layer V, whereas other layers had sparse (layer IV) or hardly any (layer I) staining. Membrane staining for CB1 was only found in axon terminals, all of which contained GABA and formed symmetric synapses. Double immunostaining also revealed that CB1-positive cells formed two neurochemically distinct subpopulations: two-thirds were cholecystokinin positive and one-third expressed calbindin, each subserving specific inhibitory functions in cortical networks. In addition, cannabinoid sensitivity of GABAergic input showed striking layer specificity, as revealed by both electrophysiological and anatomical experiments. We found a unique population of large pyramidal neurons in layer VB that received much less perisomatic innervation from CB1-expressing GABAergic axon terminals and, accordingly, showed no depolarization-induced suppression of inhibition, unlike pyramidal cells in layer II, and a population of small pyramidal cells in layer V. This suggests that inhibitory control of pyramidal cells involved in intracortical or corticostriatal processing is fine-tuned by activity-dependent endocannabinoid signaling, whereas inhibition of pyramidal cells relaying cortical information to lower subcortical effector centers often lacks this plasticity.
authors: Department of Cellular and Network Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary.
authors: Agnes L
authors: AL
authors: Bodor
authors: István
authors: I
authors: Katona
authors: Gábor
authors: G
authors: Nyíri
authors: Ken
authors: K
authors: Mackie
authors: Catherine
authors: C
authors: Ledent
authors: Norbert
authors: N
authors: Hájos
authors: Tamás F
authors: TF
authors: Freund
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D005455:Fluorescent Antibody Technique; D007395:Interneurons / Q000502:physiology*; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013003:Somatosensory Cortex / Q000166:cytology* / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D008024:Ligands; D043884:Receptor, Cannabinoid, CB1