Changes in expression of a synaptic vesicle antigen in aging sympathetic neurons

The effects of altering synaptic activity of sympathetic neurons on the expression of a synaptic vesicle protein (p65) were studied by deafferentation of the superior cervical ganglion (SCG) in adult and aged Fischer-344 rats. Levels of p65, an integral membrane protein of synaptic vesicles, were assayed by radioimmunoassay. After deafferentation, a transient increase in p65 levels is observed in the SCG of adult rats. In aged animals, the response to deafferentation is delayed and enhanced, and levels do not drop to values observed in operated adults. After SCG deafferentation, p65 levels in the iris, an SCG target, initially are depressed below control levels; p65 levels return to control values in adult animals after 14 days, but remain depressed in aged animals. In contrast, a transient increase in p65 levels is observed in the pineal of both adult and aged animals. These results suggest that while the aged sympathetic nervous system retains the ability to respond to alterations in synaptic activity, it is unable to reregulate once a response is initiated.     

Deafferentation-induced increases in a synaptic vesicle protein in the adult rat superior cervical ganglion are associated with new protein synthesis

Previous studies have shown that deafferentation of the adult rat superior cervical ganglion results in a transient increase in levels of a 65 kDa synaptic vesicle membrane protein (SV). The present study indicates that the observed increase in SV after deafferentation is the result of new protein synthesis. Treatment with cycloheximide, a protein synthesis inhibitor, for 8 h at selected times after surgery produces decreases in SV which are greater than that observed after treatment of unoperated animals. The results suggest that an increased rate of synthesis of this protein is induced by deafferentation. Transsynaptic factors may play important roles in regulation of protein synthesis in sympathetic ganglia.     

Neonatal thyroxine treatment: changes in the number of corticotropin-releasing-factor (CRF) and neuropeptide Y (NPY) containing neurons and density of tyrosine hydroxylase positive fibers (TH) in the amygdala correlate with anxiety-related behavior of wistar rats

Neonatal hyperthyroidism induces persisting alterations in the adult brain, e.g. in spatial learning and hippocampal morphology. In the present study, the relationship between anxiety-related behavior and amygdala morphology was investigated in the adult rat after transient neonatal hyperthyroidism (daily s.c. injections of 7.5 microg L-thyroxine in 0.5 ml 0.9% NaCl solution from postnatal day p1 to p12). The behavioral tests used to study anxiety-related behavior were the motility test, elevated plus-maze and fear-sensitized acoustic startle response. In the amygdala, the number of neurons containing the anxiogenic peptide corticotropin releasing factor (CRF-ir and CRF mRNA) and anxiolytic neuropeptide Y (NPY-ir), the total number of neurons and the density of tyrosine hydroxylase immunoreactive (TH-ir) fibers were quantified. Thyroxine-treated pups presented an accelerated development including opening of eyes and snout elongation as typical signs of hyperthyroidism. Thyroxine-treated adult animals displayed a reduced anxiety in the motility box and elevated plus maze, a reduction in the number of CRF-ir neurons in the central nucleus of the amygdala, as well as an increase in the number of NPY-ir neurons and density of TH-ir fibers in nuclei of the basolateral complex of the amygdala. Moreover, there was a reduction in the total number of neurons in all nuclei of the basolateral complex (despite the higher number of NPY-ir neurons), but not central nucleus of the amygdala. The number of CRF-ir neurons in the central nucleus correlated positively with anxiety-related behavior, and the number of NPY-ir neurons and the density of TH-ir fibers in the basolateral complex correlated inversely with anxiety-related behavior. The findings suggested a shift toward an anxiolytic rather than anxiogenic distribution of peptidergic neurons and fibers in the amygdala at adult age following transient neonatal hyperthyroidism.     

Neonatal synapse elimination in the rat submandibular ganglion: effect of retarded target growth

1. We have studied synapse elimination in the submandibular ganglion of neonatal rats to determine the effects of retarded target growth on synaptic development. Neurons of this ganglion provide parasympathetic innervation to the submandibular and sublingual salivary glands. 2. Ligating the main salivary ducts 2-4 days after birth at a point where nerve fibers were not damaged reduces gland weight by 55% during the 2nd wk after birth and 80% by adulthood. 3. In control animals, the average number of preganglionic inputs/neuron normally declines steadily during the first few weeks after birth, before stabilizing during the 5th wk at the control adult level. Between birth and adulthood, the number of ganglionic neurons increases by 150%. 4. Ganglia from duct-ligated animals showed an acceleration in the process of synapse elimination. Input number in experimental ganglia reached the control adult level during the 3rd wk after birth. This acceleration is confined solely to ganglia that innervate the underdeveloped glands. 5. The loss of inputs was not further enhanced by prolonged target atrophy. Thus average input numbers to neurons of 5th wk or adult experimental ganglia were not different from age-matched control values. 6. No differences from control values were seen in most cases for resting potentials, input resistances, or cell size. However, the increase in neuron number was retarded in experimental animals, and the number of synapses/neuronal profile was reduced in the adult animals. 7. Thus subnormal target growth leads to an acceleration in the process of synaptic elimination in neonatal rats. This acceleration may be mediated by alterations in the level of trophic factors emanating from the target.     

Developmental plasticity of the hypoxic ventilatory response in rats induced by neonatal hypoxia

Neonatal hypoxia alters the development of the hypoxic ventilatory response in rats and other mammals. Here we demonstrate that neonatal hypoxia impairs the hypoxic ventilatory response in adult male, but not adult female, rats. Rats were raised in 10% O₂ for the first postnatal week, beginning within 12 h after birth. Subsequently, ventilatory responses were assessed in 7- to 9-week-old unanaesthetized rats via whole-body plethysmography. In response to 12% O₂, male rats exposed to neonatal hypoxia increased ventilation less than untreated control rats (mean ± s.e.m. 35.2 ± 7.7% versus 67.4 ± 9.1%, respectively; P = 0.01). In contrast, neonatal hypoxia had no lasting effect on hypoxic ventilatory responses in female rats (67.9 ± 12.6% versus 61.2 ± 11.7% increase in hypoxia-treated and control rats, respectively; P > 0.05). Normoxic ventilation was unaffected by neonatal hypoxia in either sex at 7–9 weeks of age ( P > 0.05). Since we hypothesized that neonatal hypoxia alters the hypoxic ventilatory response at the level of peripheral chemoreceptors or the central neural integration of chemoafferent activity, integrated phrenic responses to isocapnic hypoxia were investigated in urethane-anaesthetized, paralysed and ventilated rats. Phrenic responses were unaffected by neonatal hypoxia in rats of either sex ( P > 0.05), suggesting that neonatal hypoxia-induced plasticity occurs between the phrenic nerve and the generation of airflow (e.g. neuromuscular junction, respiratory muscles or respiratory mechanics) and is not due to persistent changes in hypoxic chemosensitivity or central neural integration. The basis of sex differences in this developmental plasticity is unknown.     

Synapsin I expression in the rat retina during postnatal development

Summary The expression of the synapsin I gene was studied during postnatal development of the rat retina at the mRNA and protein levels. In situ hybridization histochemistry showed that synapsin I mRNA was expressed already in nerve cells in the ganglion cell layer of the neonatal retina, while it appeared in neurons of the inner nuclear layer from postnatal day 4 onward. Maximal expression of synapsin I mRNA was observed at P12 in ganglion cells and in neurons of the inner nuclear layer followed by moderate expression in the adult. At the protein level a shift of synapsin I appearance was observed from cytoplasmic to terminal localization during retinal development by immunohistochemistry. In early stages (P4 and P8), synapsin I was seen in neurons of the ganglion cell layer and in neurons of the developing inner nuclear layer as well as in the developing inner plexiform layer. In the developing outer plexiform layer synapsin I was localized only in horizontal cells and in their processes. Its early appearance at P4 indicated the early maturation of this cell type. A shift and strong increase of labelling to the plexiform layers at P12 indicated the localization of synapsin I in synaptic terminals. The inner plexiform layer exhibited a characteristic stratified pattern. Photoreceptor cells never exhibited synapsin I mRNA or synapsin I protein throughout development.Abbreviations GCL ganglion cell layer - INB inner neuroblast layer - INL inner nuclear layer - IPL inner plexiform layer - ONB outer neuroblast layer - ONL outer nuclear layer - OPL outer plexiform layer     

The reorganization of synaptic connexions in the rat submandibular ganglion during post-natal development.

1. The innervation of neurones in the submandibular ganglion of neonatal and adult rats has been studied with intracellular recording, and light and electron microscopy. 2. Intracellular recordings from neurones in isolated ganglia from adult animals showed that about 75% of the ganglion cells are innervated by a single preganglionic fibre. 3. However multiple steps in the post-synaptic potential (about five on average) were elicited in ganglion cells from neonatal animals by graded stimulation of the preganglionic nerve. The same result was obtained when the preganglionic fibres were stimulated at their emergence from the brainstem, indicating that neonatal neurones are innervated by several different preganglionic nerve cells. 4. The number of preganglionic fibres innervating individual ganglion cells gradually decreased during the first few weeks of life, and by about 5 weeks each ganglion cell was generally contacted by a single preganglionic axon. 5. Synapses were made on short protuberances in the immediate vicinity of the neuronal cell bodies in both neonatal and adult ganglia as shown by staining presynaptic boutons with the zinc-iodide osmium method, injection of horseradish peroxidase into ganglion cells, and electron microscopical examination. 6. Electron microscopical counts of synaptic profiles per ganglion cell perimeter showed that the number of synaptic contacts made on ganglion cells actually increased during the first few post-natal weeks, when the number of axons innervating each neurone was decreasing. 7. These results show that in the rat submandibular ganglion there is a reorganization of neuronal connexions during the first few weeks of life which results in a transition from multiple to generally single innervation of ganglion cells.     

Comparison of cross-bridge cycling kinetics in neonatal vs. adult rat ventricular muscle

The developmental shift in contractile protein isoform expression in the rodent heart likely affects actin-myosin cross-bridge interactions. We compared the Ca²⁺ sensitivity for force generation and cross-bridge cycling kinetics in neonatal (postnatal days 0–3) and adult (day 84) rats. The force-pCa relationship was determined in Triton-X skinned muscle bundles activated at pCa 9.0 to 4.0. In strips maximally activated at pCa 4.0, the following parameters of cross-bridge cycling were measured: (1) rate of force redevelopment following rapid shortening and restretching (k_tr); and (2) isometric stiffness at maximal activation and in rigor. The fraction of attached cross-bridges (_fs) and apparent rate constants for cross-bridge attachment (f_app) and detachment (g_app) were derived assuming a two-state model for cross-bridge cycling. Compared to the adult, the force-pCa curve for neonatal cardiac muscle was significantly shifted to the left. Neonatal cardiac muscle also displayed significantly smaller _fs, slower k_tr and f_app; however, g_app was not significantly different between age groups. These data indicate that weaker force production in neonatal cardiac muscle involves, at least in part, less efficient cross-bridge cycling kinetics.     

The Effects of Forelimb Deafferentation on the Post-Natal Development of Synaptic Plasticity in the Hippocampus

The effects of partial deafferentation of the forelimb on the development of long-term potentiation in the hippocampus of rats aged 13–18 days were studied. Long-term potentiation in hippocampus field CA1 was of greater amplitude and duration in control rats at 16–18 days of post-natal ontogenesis than in adult animals. Partial deafferentation by section of the median nerve in the forelimb on the 13th day of life led to the disappearance of this excess at 16–18 days. The peak in synaptic plasticity occurred later in operated animals – on day 17 – and was much less marked than in controls. The decreases in the amplitude and duration of long-term potentiation in hippocampal field CA1 in operated animals provides evidence for a decrease in the sensitivity and/or number of NMDA receptors. This suggests that partial deafferentation of one limb may lead not to a decrease but to an increase in spike and synaptic activity in the hippocampus, which in normal conditions may affect the maturation of the plastic properties of synaptic transmission associated with the expression and positions of NMDA receptors. The level of long-term potentiation in sham-operated rats was significantly greater than in controls of the same age. This significant increase in NMDA-dependent long-term potentiation may be explained by a decrease in the level of activation due to anesthesia. It is suggested that the decrease in the spike activity of cells receiving signals from the median nerve may be compensated for by activation of other specific and non-specific inputs.     

Effects of neonatal handling on the behavior and prolactin stress response in male and female rats at various ages and estrous cycle phases of females

Neonatal handling induces behavioral and hormonal changes, characterized by reduced fear in novel environments, and lesser elevation and faster return to basal levels of plasma corticosterone, prolactin and adrenaline, in response to stressors in adulthood. The present study aimed to analyze the effects of neonatal handling from Days 1 to 10 postnatal on prolactin response to ether stress in male and female rats at three life periods: neonatal, peripubertal and adulthood. Moreover, adult females were tested in two different phases of the estrous cycle, i.e., diestrus and estrus. In another set of experiments, the behavior of peripubertal and adult males and females in estrus and diestrus was analyzed in the elevated plus maze test. Pups were either handled for 1 min (handled group) or left undisturbed (nonhandled group) during the first 10 days after delivery. In adults, in the handled females in diestrus, stress induced a lesser increase in plasma prolactin compared with nonhandled ones, as in males. However, in estrus, handled females showed no difference in the prolactin response to stress. In the elevated plus maze, handled females in diestrus, but not in estrus, showed higher locomotor activity compared with nonhandled ones. Peripubertal male and female rats handled during the neonatal period showed no difference in behavior in the elevated plus maze compared with nonhandled animals. Early-life stimulation can induce long-lasting behavioral and stress-related hormonal changes, but they are not stable throughout life and phases of the estrous cycle.     

Postnatal development enhances the effects of cholinergic inputs on recruitment threshold and firing rate of rat oculomotor nucleus motoneurons

Changes in the electrophysiological and morphological characteristics of motoneurons (Mns) of the oculomotor nucleus during postnatal development have been reported, however synaptic modifications that take place concurrently with postnatal development in these Mns are yet to be elucidated. We investigated whether cholinergic inputs exert different effects on the recruitment threshold and firing rate of Mns during postnatal development. Rat oculomotor nucleus Mns were intracellularly recorded in brain slice preparations and separated in neonatal (4–7 postnatal days) and adult (20–30 postnatal days) age groups. Stimulation of the medial longitudinal fasciculus evoked a monosynaptic excitatory potential in Mns that was attenuated with atropine (1.5 μM, a muscarinic antagonist). Mns were silent at their resting membrane potential, and bath application of carbachol (10 μM, a cholinergic agonist) induced depolarization of the membrane potential and a sustained firing rate that were more pronounced in adult Mns. Pharmacological and immunohistochemical assays showed that these responses were attributable to muscarinic receptors located in the membrane of Mns. In addition, compared to control Mns, carbachol-exposed Mns exhibited a higher firing rate in response to the injection of the same amount of current, and a decrease in the current threshold required to achieve sustained firing. These latter effects were more pronounced in adult than in neonatal Mns. In conclusion, our findings suggest that cholinergic synaptic inputs are already present in neonatal Mns, and that the electrophysiological effects of such inputs on recruitment threshold and firing rate are enhanced with the postnatal development in oculomotor nucleus Mns. We propose that cholinergic input maturation could provide a greater dynamic range in adult Mns to encode the output necessary for graded muscle contraction.     

LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1.

In the CA1 region of the rat hippocampus, long-term potentiation (LTP) requires the activation of NMDA receptors (NMDARs) and leads to an enhancement of AMPA receptor (AMPAR) function. In neonatal hippocampus, this increase in synaptic strength seems to be mediated by delivery of AMPARs to the synapse. Here we studied changes in surface expression of native AMPA and NMDA receptors following induction of LTP in the adult rat brain. In contrast to early postnatal rats, we find that LTP in the adult rat does not alter membrane association of AMPARs. Instead, LTP leads to rapid surface expression of NMDARs in a PKC- and Src-family-dependent manner. The present study suggests a developmental shift in the LTP-dependent trafficking of AMPA receptors. Moreover, our results indicate that insertion of NMDA receptors may be a key step in regulating synaptic plasticity.     

Transient expression of polysynaptic NMDA receptor-mediated activity during neocortical development

During a restricted period of early postnatal development, rat neocortical neurons receive a powerful N-methyl-D-aspartate (NMDA) receptor-mediated synaptic input of variable onset latency and duration. These large-amplitude excitatory postsynaptic potentials are especially pronounced in supragranular layers and are generated by activities in polysynaptic circuits. Their occurrence in cortical slices from juvenile (postnatal (P) days 11-20), but not neonatal (P5-10) or adult (greater than or equal to P28) animals, appears to be in part a consequence of the relative immaturity of gamma-aminobutyric acid (GABA)-mediated inhibition, at a time when the requisite functional excitatory circuitry has been established. The transient manifestation of strong NMDA receptor-mediated potentials coincides temporally with a 'developmental window' within which there is enhanced sensitivity for epileptogenesis and for induction of long-term synaptic modifications in rat cortex.     

Neutrophil adhesion molecule expression in the developing neonatal rat exposed to hyperoxia

Neonatal rats have an increased tolerance to hyperoxia, which is associated with a diminished pulmonary inflammatory response compared with adults. To investigate this differing response, expression of the neutrophil adhesion molecules, L-selectin and CD18, and levels of soluble L-selectin, were examined using flow cytometry and sandwich enzyme-linked immunosorbent assay on air-exposed neonatal rat neutrophils at 0-24 and 72 h and 7, 10, 14, and 21 d of age compared with the adult and after exposure to hyperoxia (>/= 98% O2) for 56 h in adults and for 72 h and 7 d in neonates. Expression of L-selectin in 0-24-h neonates was similar to adults, but was significantly lower than adults at 72 h and 7 d (P = 0.011). Soluble L-selectin levels were significantly higher than those in adults in the 0-24- and 72-h neonates (P < 0.001). CD18 expression in unstimulated and activated neutrophils of neonatal rats was higher at 0-24 h than in the adult (P < 0.001), but thereafter did not differ from adults. After hyperoxic exposure, L-selectin did not differ between the exposure groups but soluble L-selectin tended to increase in neonates after 7 d of O2 exposure Finally, CD18 was significantly higher after hyperoxic exposure of the adult (P = 0.008), but did not change with oxygen exposure in the neonate. Based on these findings, we speculate that differences between neonatal and adult rats in expression of L-selectin may contribute to delayed oxygen toxicity in neonatal rats.     

Developmental regulation of parasympathetic nerve density by sympathetic innervation in the tarsal smooth muscle of the rat.

The developmental influence of sympathetic innervation on parasympathetic nerve density was investigated in the tarsal smooth muscle of the rat. Specificity of acetylcholinesterase staining as a marker for parasympathetic innervation was first determined by acute selective denervations. Excision of the ipsilateral superior cervical ganglion caused a 39% reduction in the density of acetylcholinesterase-positive nerves seven days later, indicating that sympathetic nerves contribute to cholinesterase-positive tarsal muscle innervation. Excision of the pterygopalatine ganglion concurrent with superior cervical ganglionectomy caused a virtually complete disappearance of acetylcholinesterase-positive innervation within seven days, indicating that non-sympathetic cholinesterase-positive fibers derive from the pterygopalatine ganglion and are presumed to be parasympathetic. Analysis of the control population indicated that parasympathetic nerve density did not vary significantly between males and females, between the superior and inferior muscles, or in rats studied at four and 12 months of age. The influence of sympathetic innervation on parasympathetic nerve density during postnatal development was examined by conducting surgical sympathectomies on postnatal day 5 and quantifying acetylcholinesterase-positive nerve density at four months of age. Neonatal sympathectomy caused a 46% reduction in cholinesterase-positive nerve density beyond that which occurred in acutely sympathectomized adult controls. It is concluded that sympathetic innervation is required for developing parasympathetic nerves to attain their normal density within the rat tarsal muscle. This finding is consistent with the idea that sympathetic nerves can exert positive effects on parasympathetic nerve outgrowth during development.     

Cochlear ablation in adult ferrets results in changes in insulin-like growth factor-1 and synaptophysin immunostaining in the cochlear nucleus

Afferent activity modulates synaptic plasticity as well as the levels of activity-dependent molecules such as growth factors. Disruption of this activity due to deafferentation has been shown to result in an altered trophic support and consequently in changes in neuronal excitability and synaptic transmission. In the present study, to test whether lack of cochlear integrity results in changes in insulin-growth factor-1 (IGF-1) and synaptophysin immunostaining in the cochlear nucleus, the first relay structure in the auditory pathway, unilateral cochlear ablations were performed in adult ferrets. Changes in IGF-1 and synaptophysin immunostaining were assessed in the anteroventral (AVCN), posteroventral (PVCN) and dorsal cochlear nucleus (DCN) at 1, 20 and 90 days after deafferentation. An increase in IGF-1 immunostaining within AVCN, PVCN and DCN was observed ipsilaterally at all survival times after cochlear ablation when compared with the contralateral side and unoperated animals. This increase was accompanied by a significant ipsilateral increase in the mean gray level of synaptophysin immunostaining as well as a decrease in the area of synaptophysin immunostaining at 1 and 20 days after the ablation in AVCN, PVCN and DCN compared with the contralateral side and control animals. These changes in synaptophysin immunostaining were no longer present 90 days after cochlear ablation. The present results provide evidence of a persistent upregulation in IGF-1 and a transitory upregulation in synaptophysin levels in the cochlear nucleus that may reflect neuroprotective mechanisms following the loss of trophic support from spiral ganglion neurons.     

Effect of early postnatal division of the postganglionic nerves on the development of principal cells and small intensely fluorescent cells in the rat superior cervical ganglion

Summary The three main postganglionic nerve branches of the superior cervical ganglion were divided on one side in 3–4-day-old rats. Five, 10, 20 and 60 days after the operation, the number of principal cells and small intensely fluorescent (SIF) cells, and the ganglion volume were estimated from a complete series of sections through each ganglion, in which catecholamines were histochemically demonstrated by formaldehyde-induced fluorescence. As compared with the contralateral, intact ganglion, the operated ganglion showed a rapid loss of principal cell bodies to about l/20th of the control value, and the normally large postnatal increase in the volume of the ganglion failed to take place in the operated ganglion. Sham operation experiments showed that these changes were due to nerve division rather than disturbed blood supply and manipulation. The number of SIF cells increased in the intact ganglia from about 200 cells/ganglion at birth and reached the adult value, about 600 cells/ganglion by the 23rd postnatal day. An essentially similar postnatal increase in SIF cell number occurred in the experimental ganglia in spite of the marked loss of principal cells. The relative number of SIF cells increased from less than 1% of all cells (SIF cells and principal cells) in the control ganglia to over 10% in the operated ganglia, in which large aggregates of SIF cells formed 20 and 60 days after nerve division. It is concluded that different sets of developmental rules may apply to the SIF cells and the principal cells.     

Interactions of inflammatory pain and morphine in infant rats: long-term behavioral effects

Neonatal rat pups exposed to repetitive acute pain show decreases in pain threshold and altered behavior during adulthood. A model using prolonged inflammatory pain in neonatal rats may have greater clinical relevance for investigating the long-term behavioral effects of neonatal pain in ex-preterm neonates. Neonatal rat pups were exposed to repeated formalin injections on postnatal (P) days 1-7 (P1-P7), with or without morphine pretreatment, and were compared with untreated controls. Behavioral testing during adulthood assessed pain thresholds using hot-plate (HP) and tail-flick (TF) tests, alcohol preference, and locomotor activity (baseline and postamphetamine). Adult rats exposed to neonatal inflammatory pain exhibited longer HP latencies than controls and male rats had longer HP thresholds compared to females. Male rats exposed to neonatal morphine alone exhibited longer TF latencies than controls. Both neonatal morphine treatment and neonatal inflammatory pain decreased ethanol preference, but their effects were not additive. During adulthood, male rats exposed to neonatal inflammatory pain exhibited less locomotor activity than untreated controls. We conclude that neonatal formalin and morphine treatment have specific patterns of long-term behavioral effects in adulthood, some of which are attenuated when the two treatments are combined.     

Developmental regulation of plasticity in the forepaw representation of ferret somatosensory cortex

This study characterized the spatiotemporal responses in ferret somatosensory cortex after sensory deprivation at different phases of cortical development. We hypothesized that cortical responses to stimulation of intact superficial radial nerve in adults will vary systematically according to maturation of thalamocortical relationships at the time of an ulnar nerve transection. Depending on the age of the animal at the time of the lesion, we found differential effects on the spatial distribution of the short- and long-latency components of the cortical response. In animals lesioned at postnatal days 5-7, when thalamic projections are not yet stabilized and layer 4 is not yet formed, we found that initial (short-latency) cortical responses are widespread and fragmented. Ulnar nerve transections performed at postnatal day 20 or 21, when thalamocortical afferents are more stabilized and layer 4 is clearly identifiable, yield moderate expansions in the distribution of short- and long-latency components of the cortical response. Nerve lesions in adults lead to a wider distribution of long-latency cortical activity. Neonatal lesions broaden the spatial distribution and increase the latency of the initial cortical response; interruption of nerve input in older juveniles alters both the early and later components; and nerve lesions in adult animals expand the distribution of later cortical activity only. These findings demonstrate correlation between developmental phase at the time sensory input is interrupted and the latency of affected components of the cortical response. This supports the hypothesis that differential response changes are regulated by functional reorganization of thalamocortical connections after neonatal lesions and alteration of corticocortical dynamics after adult lesions.     

Developmental changes in expression of GABAA receptor-channels in rat intrinsic cardiac ganglion neurones

The effects of γ-aminobutyric acid (GABA) on the electrophysiological properties of intracardiac neurones were investigated in the intracardiac ganglion plexus in situ and in dissociated neurones from neonatal, juvenile and adult rat hearts. Focal application of GABA evoked a depolarizing, excitatory response in both intact and dissociated intracardiac ganglion neurones. Under voltage clamp, both GABA and muscimol elicited inward currents at −60 mV in a concentration-dependent manner. The fast, desensitizing currents were mimicked by the GABA_A receptor agonists muscimol and taurine, and inhibited by the GABA_A receptor antagonists, bicuculline and picrotoxin. The GABA_A0 antagonist (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphonic acid (TPMPA), had no effect on GABA-induced currents, suggesting that GABA_A receptor-channels mediate the response. The GABA-evoked current amplitude recorded from dissociated neurones was age dependent whereby the peak current density measured at −100 mV was ∼20 times higher for intracardiac neurones obtained from neonatal rats (P2–5) compared with adult rats (P45–49). The decrease in GABA sensitivity occurred during the first two postnatal weeks and coincides with maturation of the sympathetic innervation of the rat heart. Immunohistochemical staining using antibodies against GABA demonstrate the presence of GABA in the intracardiac ganglion plexus of the neonatal rat heart. Taken together, these results suggest that GABA and taurine may act as modulators of neurotransmission and cardiac function in the developing mammalian intrinsic cardiac nervous system.