Interleukin-1 beta inhibits synaptic transmission and induces membrane hyperpolarization in amygdala neurons.
Interleukin-1 beta (IL-1 beta), a mediator of immune response, is found in the brain and IL-1 binding sites are located in the basolateral amygdala (BLA). Superfusion of IL-1 beta (118 pM) hyperpolarized the membrane and decreased input resistance in most BLA neurons in brain slice preparations. The hyperpolarization was dose dependent, reversible, persisted in tetrodotoxin and had an estimated EC50 of 15.3 pM. Reversal potentials for the hyperpolarization recorded with potassium acetate and KCl electrodes were -74 and -40 mV, respectively. These data suggest involvement of a chloride conductance. The hyperpolarization was not observed in bicuculline or in acutely dissociated BLA neurons, which implicates an indirect mediation through enhancement of endogenous gamma-aminobutyric acid (GABA). Superfusion of IL-1 beta (118 pM) inhibited excitatory and fast and slow inhibitory postsynaptic potentials evoked by stimulating either the stria terminalis or the lateral amygdala. Fast and slow inhibitory postsynaptic potentials elicited by direct stimulation of GABA interneurons in the lateral amygdala were also depressed by IL-1 beta. IL-1 beta did not depress responses to GABA or glutamate receptor agonists in slices or currents induced by glutamate agonists in acutely dissociated BLA neurons. These findings indicate that inhibition of synaptic transmission is presynaptic. The results show that IL-1 beta inhibits excitatory and inhibitory transmission at a presynaptic site and hyperpolarizes the membrane through an indirect action, possibly by enhancing the action of endogenous GABA in the BLA nucleus. The inhibitory effect of IL-1 beta suggests that factors in the immune system play a role in modulating neuronal function in the BLA.
Yu
B
B
Department of Pharmacology and Toxicology, University of Texas, Medical Branch at Galveston.
Shinnick-Gallagher
P
P
D000595:Amino Acid Sequence; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D007375:Interleukin-1; D011963:Receptors, GABA-A; D009118:Muscimol; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid