Abstract
The hippocampus is thought to encode information by altering synaptic strength via synaptic plasticity. Some forms of synaptic plasticity are induced by lipid-based endocannabinoid signaling molecules that act on cannabinoid receptors (CB1). Endocannabinoids modulate synaptic plasticity of hippocampal pyramidal cells and stratum radiatum interneurons; however, the role of endocannabinoids in mediating synaptic plasticity of stratum oriens interneurons is unclear. These feedback inhibitory interneurons exhibit presynaptic long-term potentiation (LTP), but the exact mechanism is not entirely understood. We examined whether oriens interneurons produce endocannabinoids, and whether endocannabinoids are involved in presynaptic LTP. Using patch-clamp electrodes to extract single cells, we analyzed the expression of endocannabinoid biosynthetic enzyme mRNA by reverse transcription and then real-time PCR (RT-PCR). The cellular expression of calcium-binding proteins and neuropeptides were used to identify interneuron subtype. RT-PCR results demonstrate that stratum oriens interneurons express mRNA for both endocannabinoid biosynthetic enzymes and the type I metabotropic glutamate receptors (mGluRs), necessary for endocannabinoid production. Immunohistochemical staining further confirmed the presence of diacylglycerol lipase alpha, an endocannabinoid-synthesizing enzyme, in oriens interneurons. To test the role of endocannabinoids in synaptic plasticity, we performed whole-cell experiments using high-frequency stimulation to induce long-term potentiation in somatostatin-positive cells. This plasticity was blocked by AM-251, demonstrating CB1-dependence. In addition, in the presence of a fatty acid amide hydrolase inhibitor (URB597; 1 µM) and MAG lipase inhibitor (JZL184; 1 µM) that increase endogenous anandamide and 2-arachidonyl glycerol, respectively, excitatory current responses were potentiated. URB597-induced potentiation was blocked by CB1 antagonist AM-251 (2 µM). Collectively, this suggests somatostatin-positive oriens interneuron LTP is CB1-dependent.
Highlights
Synaptic plasticity is a process whereby synapses can be strengthened or weakened by either presynaptically altering neurotransmitter release, or postsynaptically modifying synaptic receptor numbers
We employed whole-cell patch clamp electrophysiology to identify plasticity of stratum oriens interneurons followed by real-time PCR (RT-PCR) on the extracted cell to examine mRNA components involved in endocannabinoid biosynthesis
This is the first demonstration of CB1-dependence for stratum oriens interneuron long-term potentiation (LTP) and of eCB
Summary
Synaptic plasticity is a process whereby synapses can be strengthened or weakened by either presynaptically altering neurotransmitter release, or postsynaptically modifying synaptic receptor numbers. Plasticity is a critical attribute that allows for brain modification in an experience-dependent fashion, with the hippocampus encoding and consolidating memory. Two major synaptic plasticity forms exhibited in the brain are long-term potentiation (LTP) [1] and long-term depression (LTD) [2]. Hippocampal LTP of cornu ammonis (CA1) pyramidal cells is dependent on N-methyl-D-aspartate (NMDA) glutamate receptors, which induce LTP by triggering a signal cascade that results in the insertion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors into the postsynaptic membrane [3]. Other NMDA receptor-independent forms of plasticity occur that are mediated by various mechanisms including lipid messengers known as endocannabinoids (eCBs).
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