title: Functional and molecular development of striatal fast-spiking GABAergic interneurons and their cortical inputs.
abstract: Despite their small number, fast-spiking (FS) GABAergic interneurons play a critical role in controlling striatal output by mediating cortical feed-forward inhibition of striatal medium-sized spiny (MS) projection neurons. We have examined the functional development of FS interneurons and their cortical inputs, and the expression of three of their molecular markers, in the dorsolateral rat striatum between postnatal days (P)12--14 and 19--23, the time of major corticostriatal synaptogenesis. FS interneurons were visualized with infrared differential interference contrast (IR-DIC) optics and examined with current-clamp recording in the presence of the GABA(A) receptor antagonist bicuculline methiodide. FS interneurons displayed action potentials at relatively high frequencies in response to depolarizing current pulses by P12, but developmental changes occurred in action potential and afterhyperpolarization duration and amplitude and input resistance between P12--14 and P19--23, as well as an increase in maximum firing frequency in response to depolarizing current pulses. Maturation in electrophysiological properties was paralleled by increases in Kv 3.1 and parvalbumin mRNA expression, while GAD-67 mRNA levels remained constant. Furthermore, FS interneurons in the younger age group responded to stimulation of cortical afferents with excitatory postsynaptic potentials (EPSPs) of higher amplitudes and received significantly more spontaneous depolarizing inputs than did MS neurons. Thus, FS interneurons are under frequent and continuous cortical influence by the end of the 2nd postnatal week, a time when corticostriatal synapses are sparse, suggesting that they may provide a major inhibitory influence in the striatum during the period of intense developmental maturation.
authors.affiliation: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1769, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Plotkin
authors.forename: Nanping
authors.initials: N
authors.lastname: Wu
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Chesselet
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology* / Q000254:growth & development; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization / Q000379:methods; D007395:Interneurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018756:GABA Antagonists; D007527:Isoenzymes; D010320:Parvalbumins; D012333:RNA, Messenger; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D001640:Bicuculline