Neuronal activity influences the growth of barrels in developing rat primary somatosensory cortex without affecting the expression pattern of four major GABAA receptor alpha subunits.
Thalamic innervation plays a major role in parcellation of neocortex and maturation of cortical circuits. While the underlying mechanisms are unknown, lesion studies have identified GABAA receptors in neocortex as molecular targets of thalamic regulation [J. Paysan, A. Kossel, J. Bolz, J.M. Fritschy, Area-specific regulation of gamma-aminobutyric acid A receptor subtypes by thalamic afferents in developing rat neocortex, Proc. Natl. Acad. Sci. USA 94 (1997) 6995-7000]. To determine the factors regulating the expression of GABAA receptors, the overall level of neuronal activity was chronically modulated in neonatal rat cortex. Slices of Elvax polymer loaded with the N-methyl-D-asparate (NMDA) receptor antagonist MK-801 or with brain derived neurotrophic factor (BDNF) were placed unilaterally over the left parietal cortex in newborn animals. Unlike thalamic lesions (Paysan et al., 1997), these chronic drug treatments did not alter the laminar distribution or the expression level of the four major GABAA receptor alpha subunit isoforms (alpha 1, alpha 2, alpha 3, alpha 5) in primary somatosensory cortex (S1), as assessed immunohistochemically after one week. In particular, the staining of the barrel field in layers III-IV, which is very prominent with the alpha 1-subunit, was preserved in the drug-treated hemisphere. Even systemic administration of MK-801 at birth, which resulted in pronounced retardation of cortical development, had no effect on the laminar distribution and staining intensity of the four GABAA receptor alpha subunit variants. However, the size of barrels in S1, as measured in tangential sections stained for the GABAA receptor alpha 1 subunit, was enlarged upon chronic, topical blockade of NMDA receptors with MK-801 and was reduced to the same extent upon chronic exposure to BDNF. Thus, these pharmacological treatments modulated cortical growth, possibly by exerting opposite effects on neuronal activity in S1. The results suggest that the parcellation of somatosensory cortex and the laminar distribution of GABAA receptor subtypes are governed primarily by factors independent of thalamocortical activity.
Penschuck
S
S
Institute of Pharmacology, University of Zurich, Switzerland.
Giorgetta
O
O
Fritschy
J M
JM
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D007536:Isomerism; D009474:Neurons / Q000502:physiology*; D011145:Polyvinyls; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013003:Somatosensory Cortex / Q000254:growth & development* / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects