GABAergic and glycinergic circuits are found throughout the auditory brainstem, and it is generally assumed that transmitter phenotype is established early in development. The present study documents a profound transition from GABAergic to glycinergic transmission in the gerbil lateral superior olive (LSO) during the first 2 postnatal weeks. Whole-cell voltage-clamp recordings were obtained from LSO neurons in a brain slice preparation, and IPSCs were evoked by electrical stimulation of the medial nucleus of the trapezoid body (MNTB), a known glycinergic projection in adult animals. GABAergic and glycinergic components were identified by blocking transmission with bicuculline and strychnine (SN), respectively. In the medial limb of LSO, there was a dramatic change in the GABAergic IPSC component, decreasing from 78% at postnatal day 3 (P3)-P5 to 12% at P12-P16. There was an equal and opposite increase in the glycinergic component during this same period. Direct application of GABA also elicited significantly larger amplitude and longer duration responses in P3-P5 neurons compared with glycine-evoked responses. In contrast, MNTB-evoked IPSCs in lateral limb neurons were more sensitive to SN throughout development. Consistent with the electrophysiological observations, there was a reduction in staining for the beta2,3-GABAA receptor subunit from P4 to P14, whereas staining for the glycine receptor-associated protein gephyrin increased. Brief exposure to baclofen depressed transmission at excitatory and inhibitory synapses for approximately 15 min, suggesting a GABAB-mediated metabotropic signal. Collectively, these data demonstrate a striking switch from GABAergic to glycinergic transmission during postnatal development. Although GABA and glycine elicit similar postsynaptic ionotropic responses, our results raise the possibility that GABAergic transmission in neonates may play a developmental role distinct from that of glycine.

The morphology of the mature motor neuron dendritic arbor is determined by activity-dependent processes occurring during a critical period in early postnatal life. The abundance of the AMPA receptor subunit GluR1 in motor neurons is very high during this period and subsequently falls to a negligible level. To test the role of GluR1 in dendrite morphogenesis, we reintroduced GluR1 into rat motor neurons at the end of the critical period and quantitatively studied the effects on dendrite architecture. Two versions of GluR1 were studied that differed by the amino acid in the "Q/R" editing site. The amino acid occupying this site determines single-channel conductance, ionic permeability, and other essential electrophysiologic properties of the resulting receptor channels. We found large-scale remodeling of dendritic architectures in a manner depending on the amino acid occupying the Q/R editing site. Alterations in the distribution of dendritic arbor were not prevented by blocking NMDA receptors. These observations suggest that the expression of GluR1 in motor neurons modulates a component of the molecular substrate of activity-dependent dendrite morphogenesis. The control of these events relies on subunit-specific properties of AMPA receptors.

Basic fibroblast growth factor (Fgf2) is required for the generation of founder cells within the dorsal pseudostratified ventricular epithelium, which will generate the cerebral cortex, but the ganglionic eminences are not affected. We report here that the Fgf2 null mutant mice show an ϳ40% decrease in cortical glutamatergic pyramidal neurons. In contrast, no change in pyramidal or granule cell number is detected in the hippocampus of Fgf2 Ϫ/Ϫ mice. In addition, the soma of the pyramidal cells in the frontal and parietal cortices are smaller in Fgf2 knock-out mice. The decrease in the number and size of glutamatergic neuronal population affects all cortical layers but is restricted to the frontal and parietal cortices without any change in the occipital cortex, indicating that Fgf2 is necessary to regulate cell number and size in the anterior cerebral cortex. In contrast to pyramidal neurons, cortical GABA interneurons are unaffected by the lack of Fgf2. The resulting imbalance between the excitatory and inhibitory neurotransmission in the cerebral cortex is reflected by an increased duration of sleep when the animals receive a GABA receptor agonist. Thus, Fgf2 signaling may contribute to the regional specification of the cerebral cortex and may play a role in increasing the size of anterior cortical regions during vertebrate evolution.

Fibroblast growth factor receptor (FGFR) gene products (Fgfr1,Fgfr2Behaviorally, tFgfr1 transgenic mice displayed spontaneous and persistent locomotor hyperactivity that apparently was not attributable to alterations in subcortical monoaminergic systems, because transgenic animals responded to both amphetamine and guanfacine, an ␣2A adrenergic receptor agonist. We conclude that FGF tyrosine kinase signaling may be required for the genesis and growth of pyramidal neurons in frontal and temporal cortical areas, and that alterations in cortical development attributable to disrupted FGF signaling are critical for the inhibitory regulation of motor behavior.

Inhibitory synaptic transmission is known to play an important role during the maturation of central auditory pathways. While there is a lot of information on the modulatory role of glycine (Gly) on the postsynaptic target nuclei in the developing auditory brain stem, such a role for gamma‐aminobutyric acid (GABA) in the lateral superior olive (LSO) of neonatal gerbil has been only recently reported (Kotak and Sanes [1997] Soc Neurosci Abst 23:1549; Kotak et al. [1998] J Neurosci 18:4646–4655). Here we present further immunohistochemical findings and the first ultrastructural evidence documenting a significant decrease in the postsynaptic localization of the β2,3 subunit of the GABAA receptor from postnatal day (P)4 to P14 in the LSO of gerbil and the shift in the location of most of the staining from dendritic to astroglial over the same time course. There was a concomitant increase in staining for the Gly receptor (GlyR) anchoring protein, gephyrin. At the same time, GABA and Gly did not show a significant change in their staining pattern, suggesting that the transmitter levels are not particularly indicative of the inhibitory function in the neonatal gerbil LSO, but their receptors on the postsynaptic cells are. The observations of the present study suggest that the early GABAergic inhibition may be important in establishing appropriate synaptic contacts in the LSO of gerbil. J. Comp. Neurol. 409:664–681, 1999. © 1999 Wiley‐Liss, Inc.