Postnatal maturation of the GABAergic system in rat neocortex.
1. The postnatal maturation of intracortical inhibitory circuitry and the development of responses to applied gamma-aminobutyric acid (GABA) and baclofen were studied in pyramidal and nonpyramidal neurons from layers II and III of the rat primary somatosensory and primary visual cortex, in vitro. 2. Depolarizing spontaneous inhibitory postsynaptic potentials (IPSPs) could be recorded in approximately 70% of the young (postnatal day 4-10; P4-10), juvenile (P11-16), and adult cells (P28-41), respectively, when they were loaded with nitrate. At all ages these spontaneous events could be blocked by application of the GABAA receptor antagonist bicuculline methiodide (BMI), indicating that they were mediated by activation of GABAA receptors. 3. In 122 of the 130 adult cells tested, standardized electrical stimulation of the white matter or layer VI evoked a brief excitatory postsynaptic potential (EPSP), followed by both a fast (f-) and a long-latency (l-)IPSP. Similar stimuli evoked a biphasic IPSP in only 51 of the 98 juvenile and in only 1 of the 56 young neurons studied. The mean peak conductance of the f-IPSP and the l-IPSP increased significantly from 50.2 and 7.5 nS, respectively, in juvenile cells to 84.2 and 18.0 nS, respectively, in adult neurons. 4. Application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-phosphonovaleric acid (D-APV) to juvenile cells induced a significant negative shift in the reversal potential of both the f-IPSP and l-IPSP. This effect was accompanied by a reduction in the peak conductance during these events by 31 and 48%, respectively, indicating that a prominent long-lasting NMDA receptor-mediated EPSP occurs concurrent with the early and late IPSP in immature neurons. In adult neurons, D-APV had no significant effect on the reversal potential of the f- and l-IPSP, although the peak conductance decreased by 20 and 5%, respectively, suggesting that there was a smaller concurrent activation of NMDA receptors in this age group. 5. The functional maturation of GABAA and GABAB receptors was studied using focal applications of GABA to the soma and the apical dendrite. Somatic GABA applications to adult neurons held at depolarized membrane potentials evoked a triphasic response, consisting of 1) a GABAA-mediated hyperpolarizing fast component (GABAhf; reversal potential, -76 mV), 2) a GABAA-mediated depolarizing phase (GABAd; -54 mV), and 3) a hyperpolarizing late response (GABAhl; -80 mV). The GABAd response could be demonstrated at all ages in almost every neuron.(ABSTRACT TRUNCATED AT 400 WORDS)
Luhmann
H J
HJ
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, California 94305.
Prince
D A
DA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002540:Cerebral Cortex / Q000254:growth & development / Q000502:physiology*; D002712:Chlorides / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; D001640:Bicuculline