This study documents the variation in the amino acid neurotransmitter contents during mouse parietal cortex development, from embryonic day 13 (E13) until young adulthood, between postnatal day 21 (P21) and P30. Taurine, an inhibitory neurotransmitter and neuromodulator, is the most abundant neurotransmitter in the developing neocortex, whereas, at the adult stage, glutamate is the more prominent neurotransmitter playing an excitatory role, and GABA is the major inhibitory neurotransmitter. During the proliferative stage of neurogenesis in the mouse cerebral cortex, between E13 and E17, relatively high levels of glutamate, aspartate, taurine and glycine were detected, consistent with a possible trophic influence of these neurotransmitters during cortical development prior to synaptogenesis. Between E17 and E19, a significant decline in the contents of these neurotransmitters was observed, consistent with earlier reports of cell death in the ventricular and subventricular zones during this stage of development. During the perinatal period, a progressive increment in glutamate level was seen between E21 and P5, and then the values remained constant until the second postnatal week. Glutamate also decreased by about 25% between P11 and P15, on the other hand, aspartate diminished by about 20% between P7 and P9. These results were consistent with previous reports of histogenetic cell death during the first 2 postnatal weeks in mouse neocortex. GABA increased from the embryonic period until young adulthood, in contrast, the glycine content decreased; thus, in the adult parietal cortex, the GABA content was about 2.6-fold higher than that of glycine. During the first postnatal week, the concentrations of glutamate and GABA showed significant increments between P0 and P5, while those of aspartate and glycine remained constant. During this period, amino acids are predominantly excitatory and the cerebral cortex is vulnerable to epileptiform activity; the significant increment in taurine content between P0 and P3 suggests a neuroprotective action of taurine against excitotoxicity. At P15, coinciding with the period of maximum cortical synaptogenesis, significant increments in GABA and glycine contents were observed which could be related to the maturation of inhibitory synaptic transmission. At the young adult stage, there was a rise in the levels of both excitatory neurotransmitters, glutamate and aspartate, and a significant reduction in the contents of all three inhibitory neurotransmitters, GABA, glycine and taurine.

The variation in the levels of excitatory (glutamate and aspartate) and inhibitory (GABA, glycine and taurine) neurotransmitters during neurogenesis in mouse cerebellum, from embryonic day (E) 15 until the young adult stage, was analyzed by high-pressure liquid chromatography. Between E15 and E21, high contents of GABA, glutamate and aspartate were detected, with the GABA levels approximately 2- to 3-fold higher than those of glutamate and aspartate. After birth, the levels of GABA remained high during the first 2 postnatal weeks and then reached a plateau comparable to adult values by the third week. The levels of glutamate and aspartate increased gradually from birth to the young adult stage, showing peak values at postnatal days (P) 3 and P11. Glycine and taurine were present at relatively low concentrations during the prenatal period, then rose significantly by about 4-fold after birth; their levels decreased by the end of the first postnatal week but increased gradually thereafter until reaching adult values by the third week. To determine the endogenous neurotransmitter production in the cerebellar cortex, primary histotypic cerebellar cultures prepared at P10 were analyzed and the in vitro transmitter contents were compared with the adult in situ values. The cultures showed about the same levels of glutamate and aspartate; however, their concentrations were lower by half than in vivo, suggesting that both play an equally important role in the excitatory neurotransmission of the cerebellar cortex internal circuitry pathways and that in mature cerebellum, about 50% of the excitatory synaptic inputs derive from the afferent climbing and mossy fibers. The in vitro GABA and glycine contents were comparable with the in vivo levels, whereas the taurine concentrations were about 5-fold lower in vitro than in vivo. These findings indicate that most of the GABA and glycine transmitters are produced intrinsically while a high proportion of taurine in the cerebellum comes from extracerebellar afferents. This study provides data on the changing levels of the amino acid neurotransmitters in developing mouse cerebellum and the relative proportions of neurotransmitter contents that are produced by intrinsic neurons in contrast to those derived from extrinsic afferent fibers.

The variation in the levels of the monoamine and amino acid neurotransmitters was studied during the period of neurogenesis in male mouse hypothalamus, from embryonic day 15 until the age of young adult. The results shown in this study demonstrate that the monoamines appear early in the fetal brain and that the maximum expression of the catecholaminergic system, particularly that of dopamine, occurs during the late neonatal period or mouse infancy, when the role played by the catecholamines on the maturation of the neurosecretory systems is more significant. In relation to the amino acid neurotransmitters, glutamate and taurine seem to be the principal transmitters of the hypothalamus since their concentrations were about five-tenfold higher than the levels of glycine and GABA. Both amino acids had the same pattern of variation during development, showing elevated values during the prenatal, late neonatal and early pubertal period. Increased concentrations of the inhibitory neurotransmitter GABA were observed on the day before birth, at the end of the neonatal period and throughout the prepubertal period, suggesting that the influence of GABA on hypothalamic neurogenesis increases by the time when the hypothalamic nuclei have reached maturity and the local circuits have been established. To determine the intrinsic neurotransmitter production, primary hypothalamic histotypic cultures prepared from mice at postnatal days 8-10 were analyzed for their content of neurotransmitters. The in vitro analysis revealed that the hypothalamic neurons intrinsically produce dopamine, glutamate, taurine and glycine in homologable amounts with those of young adult animals. The comparative analysis also showed that about 50% of the GABA content and less than 5% of the hypothalamic epinephrine level are locally produced, while serotonin comes mainly from extrinsically located neurons.

The developmental changes in the levels of amino acid neurotransmitters were analyzed by high pressure liquid chromatography during mouse olfactory bulb neurogenesis, from embryonic day (E)13 until the young adult age, between postnatal days (P)30 and P40. During the embryonic period, high levels of glutamate, aspartate and GABA were observed, with the values of GABA about 2-fold higher than those of glutamate and aspartate. At P0, the production of these neurotransmitters experienced birth stress as shown by a significant 2-fold reduction in their levels. During the first two postnatal weeks, a progressive increase in the glutamate content was detected diminishing slightly in the adult stage. The aspartate concentrations showed a maximal value at P3 and then decreased gradually until the second postnatal week; in the young adult age, its concentration was comparable with that of glutamate. The postnatal GABA contents increased progressively from birth to maturity, showing maximal levels at P3, P11 and in the adult. Throughout the studied developmental period, the concentration of glycine remained relatively low. With regard to taurine, very low concentrations were detected during the prenatal period but after birth, the taurine content gradually increased with age, and in the adult animal, its concentration was comparable with those of GABA and glutamate. Our data demonstrate the predominance of GABA and glutamate during olfactory bulb synaptogenesis, however, in the adult animal, both glutamate and aspartate exert the same influence in the excitatory synaptic transmission; in the adult inhibitory synaptic transmission, taurine appears to play an important neuromodulatory or neurotransmitter role as that of GABA. To determine the intrinsic neurotransmitter production, primary histotypic olfactory bulb cultures were prepared from mice at P10. The comparative analysis of in vitro neurotransmitter contents with those in in situ adult animal showed higher levels of endogenously produced glutamate, glycine and GABA in the olfactory bulb than the extrinsic ones coming from olfactory nerve axons and higher olfactory brain centers. On the other hand, most of aspartate and taurine neurotransmitters apparently come from extrinsically located neurons.

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