Sulforhodamine 101 induces long-term potentiation of intrinsic excitability and synaptic efficacy in hippocampal CA1 pyramidal neurons

• Published in: Neuroscience 2010-09, Vol.169 (4), p.1601-1609
• Main Authors: Kang, J, Kang, N, Yu, Y, Zhang, J, Petersen, N, Tian, G.F, Nedergaard, M
• Format: Article
• Language: English
• Subjects: Action potential; action potential threshold; Animals; Biological and medical sciences; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - physiology; Convulsants - pharmacology; EPSC; Fundamental and applied biological sciences. Psychology; intrinsic excitability; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Neurology; NMDA receptor; Organ Culture Techniques; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Rats; Rats, Sprague-Dawley; Rhodamines - pharmacology; seizure; SR101 dye; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.06.020

Abstract Sulforhodamine 101 (SR101) has been extensively used for investigation as a specific marker for astroglia in vivo and activity-dependent dye for monitoring regulated exocytosis. Here, we report that SR101 has bioactive effects on neuronal activity. Perfusion of slices with SR101 (1 μM) for 10 min induced long-term potentiation of intrinsic neuronal excitability (LTP-IE) and a long-lasting increase in evoked EPSCs (eEPSCs) in CA1 pyramidal neurons in hippocampal slices. The increase in intrinsic neuronal excitability was a result of negative shifts in the action potential (AP) threshold. The N-methyl d -aspartate receptor (NMDAR) antagonist, AP-5 (50 μM), blocked SR101-induced LTP-IE, but glutamate receptor blockers, AP-5 (50 μM), MCPG (200 μM), and MSOP (100 μM), only partially blocked SR101-induced potentiation of eEPSCs. SR101 induced an enhancement of evoked synaptic NMDAR currents, suggesting that SR101 enhances activation of synaptic NMDARs. SR101-induced LTP-IE and potentiation of synaptic transmission triggered spontaneous neuronal firing in slices and in vivo epileptic seizures. Our results suggest that SR101 is an epileptogenic agent that long-lastingly lowers the AP threshold to increase intrinsic neuronal excitability and enhances the synaptic efficacy to increase synaptic inputs. As such, SR101 can be used as an experimental tool to induce epileptic seizures.