Pathway-specific targeting of GABA(A) receptor subtypes to somatic and dendritic synapses in the central amygdala.
Neurons in the central amygdala express two distinct types of ionotropic GABA receptor. One is the classical GABA(A) receptor that is blocked by low concentrations of bicuculline and positively modulated by benzodiazepines. The other is a novel type of ionotropic GABA receptor that is less sensitive to bicuculline but blocked by the GABA(C) receptor antagonist (1,2,5,6-tetrohydropyridine-4-yl) methylphosphinic acid (TPMPA) and by benzodiazepines. In this study, we examine the distribution of these two receptor types. Recordings of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) showed a wide variation in amplitude. Most events had amplitudes of < 50 pA, but a small minority had amplitudes >100 pA. Large-amplitude events also had rise times faster than small-amplitude events. Large-amplitude events were fully blocked by 10 microM bicuculline but unaffected by TPMPA. Small amplitude events were partially blocked by both bicuculline and TPMPA. Focal application of hypertonic sucrose to the soma evoked large-amplitude mIPSCs, whereas focal dendritic application of sucrose evoked small-amplitude mIPSCs. Thus inhibitory synapses on the dendrites of neurons in the central amygdala express both types of GABA receptor, but somatic synapses expressed purely GABA(A) receptors. Minimal stimulation revealed that inhibitory inputs arising from the laterally located intercalated cells innervate dendritic synapses, whereas inhibitory inputs of medial origin innervated somatic inhibitory synapses. These results show that different types of ionotropic GABA receptors are targeted to spatially and functionally distinct synapses. Thus benzodiazepines will have different modulatory effects on different inhibitory pathways in the central amygdala.
Delaney
A J
AJ
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra.
Sah
P
P
D000679:Amygdala / Q000166:cytology* / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003712:Dendrites / Q000737:chemistry / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D018408:Patch-Clamp Techniques; D010721:Phosphinic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology
C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D018756:GABA Antagonists; C087200:GABA-C receptor; D010721:Phosphinic Acids; D011725:Pyridines; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline