Chronic adolescent morphine exposure alters the responses of lateral paragigantocellular neurons to acute morphine administration in adulthood.

Accumulating evidence support the growing non-medical use of morphine during adolescence. Despite this concern which has recently been addressed in some studies, cellular mechanisms underlying the long-term neurobiological and behavioral effects of opiate exposure during this critical period have still remained largely unexplored. Several reports have proposed that subtle long-lasting neurobiological alterations might be triggered by exposure to opiate derivatives or drugs of abuse particularly when this occurs during a critical phase of brain maturation such as adolescence. The present study was designed to investigate how chronic adolescent morphine exposure could affect the responsiveness of lateral paragigantocellular (LPGi) neurons to acute morphine administration in adult rats. Male Wistar rats received chronic escalating morphine or saline during adolescence (30-39d) for 10 days. During adulthood (65d), the extracellular unit activities of LPGi neurons were recorded in urethane-anesthetized animals. Results indicated that adolescent morphine treatment enhances the baseline activity of LPGi neurons. In addition, morphine-induced inhibition of spontaneous discharge rate was potentiated in adult rats received morphine during adolescence. However, this pretreatment did not affect the extent of morphine excitatory effect, onset or peak of cellular response and regularity of unit discharge in LPGi neurons. Our study supports the hypothesis that adolescent morphine exposure induces long-lasting neurophysiological alterations in brain regions known to play a role in mediating opiate effects. This finding sheds light on the possible effect of opiate pre-exposure on addiction susceptibility in future.

A hindbrain segmental scaffold specifying neuronal location in the adult goldfish, Carassius auratus.

The vertebrate hindbrain develops as a series of well-defined neuroepithelial segments or rhombomeres. While rhombomeres are visible in all vertebrate embryos, generally there is not any visible segmental anatomy in the brains of adults. Teleost fish are exceptional in retaining a rhombomeric pattern of reticulospinal neurons through embryonic, larval, and adult periods. We use this feature to map more precisely the segmental imprint in the reticular and motor basal hindbrain of adult goldfish. Analysis of serial sections cut in three planes and computer reconstructions of retrogradely labeled reticulospinal neurons yielded a segmental framework compatible with previous reports and more amenable to correlation with surrounding neuronal features. Cranial nerve motoneurons and octavolateral efferent neurons were aligned to the reticulospinal scaffold by mapping neurons immunopositive for choline acetyltransferase or retrogradely labeled from cranial nerve roots. The mapping corresponded well with the known ontogeny of these neurons and helps confirm the segmental territories defined by reticulospinal anatomy. Because both the reticulospinal and the motoneuronal segmental patterns persist in the hindbrain of adult goldfish, we hypothesize that a permanent "hindbrain framework" may be a general property that is retained in adult vertebrates. The establishment of a relationship between individual segments and neuronal phenotypes provides a convenient method for future studies that combine form, physiology, and function in adult vertebrates.

[Functional state of adolescents with high and low stress reactivity under informational load].

The analysis of a complex psycho-physiological set of changes of 13-14 year-old adolescents with high and low stress reactivity under the circumstances of informational loads of different complex levels showed that the test tasks rise their level of CNS activity, the autonomic balance shift to the predominance of the sympathetic part of ANS and system circulatory dynamics stimulation. It is stated that at the beginning the rise of psycho-physiological reactivity under a tense informational load of boys' sexual maturation levels (SML) of a particular typological groups is coming up. It shows a high physiological cost of adaptation and low functional capabilities of adolescents' organisms who are under II and III SML. It is also stated that there are some valuable differences between the adolescents with high and low stress reactivity on the considering SML which are conditioned by the specific of cortical-stem and limbic-reticulated mechanisms of functional state regulation.

Synaptic plasticity at intrathalamic connections via CaV3.3 T-type Ca2+ channels and GluN2B-containing NMDA receptors.

The T-type Ca(2+) channels encoded by the Ca(V)3 genes are well established electrogenic drivers for burst discharge. Here, using Ca(V)3.3(-/-) mice we found that Ca(V)3.3 channels trigger synaptic plasticity in reticular thalamic neurons. Burst discharge via Ca(V)3.3 channels induced long-term potentiation at thalamoreticular inputs when coactivated with GluN2B-containing NMDA receptors, which are the dominant subtype at these synapses. Notably, oscillatory burst discharge of reticular neurons is typical for sleep-related rhythms, suggesting that sleep contributes to strengthening intrathalamic circuits.

The serotonergic anatomy of the developing human medulla oblongata: implications for pediatric disorders of homeostasis.

The caudal serotonergic (5-HT) system is a critical component of a medullary "homeostatic network" that regulates protective responses to metabolic stressors such as hypoxia, hypercapnia, and hyperthermia. We define anatomically the caudal 5-HT system in the human medulla as 5-HT neuronal cell bodies located in the raphé (raphé obscurus, raphé magnus, and raphé pallidus), extra-raphé (gigantocellularis, paragigantocellularis lateralis, intermediate reticular zone, lateral reticular nucleus, and nucleus subtrigeminalis), and ventral surface (arcuate nucleus). These 5-HT neurons are adjacent to all of the respiratory- and autonomic-related nuclei in the medulla where they are positioned to modulate directly the responses of these effector nuclei. In the following review, we highlight the topography and development of the caudal 5-HT system in the human fetus and infant, and its inter-relationships with nicotinic, GABAergic, and cytokine receptors. We also summarize pediatric disorders in early life which we term "developmental serotonopathies" of the caudal (as well as rostral) 5-HT domain and which are associated with homeostatic imbalances. The delineation of the development and organization of the human caudal 5-HT system provides the critical foundation for the neuropathologic elucidation of its disorders directly in the human brain.

Properties of synaptic transmission from the reticular formation dorsal to the facial nucleus to trigeminal motoneurons during early postnatal development in rats.

We previously reported that electrical stimulation of the reticular formation dorsal to the facial nucleus (RdVII) elicited excitatory masseter responses at short latencies and that RdVII neurons were antidromically activated by stimulation of the trigeminal motor nucleus (MoV), suggesting that excitatory premotor neurons targeting the MoV are likely located in the RdVII. We thus examined the properties of synaptic transmission from the RdVII to jaw-closing and jaw-opening motoneurons in horizontal brainstem preparations from developing rats using voltage-sensitive dye, patch-clamp recordings and laser photostimulation. Electrical stimulation of the RdVII evoked optical responses in the MoV. Combined bath application of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV) reduced these optical responses, and addition of the glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline further reduced the remaining responses. Electrical stimulation of the RdVII evoked postsynaptic currents (PSCs) in all 19 masseter motoneurons tested in postnatal day (P)1-4 rats, and application of CNQX and the NMDA receptor antagonist (+/-)-3(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced the PSC amplitudes by more than 50%. In the presence of CNQX and CPP, the GABA(A) receptor antagonist SR95531 further reduced PSC amplitude, and addition of strychnine abolished the remaining PSCs. Photostimulation of the RdVII with caged glutamate also evoked PSCs in masseter motoneurons of P3-4 rats. In P8-11 rats, electrical stimulation of the RdVII also evoked PSCs in all 14 masseter motoneurons tested, and the effects of the antagonists on the PSCs were similar to those in P1-4 rats. On the other hand, RdVII stimulation evoked PSCs in only three of 16 digastric motoneurons tested. These results suggest that both neonatal and juvenile jaw-closing motoneurons receive strong synaptic inputs from the RdVII through activation of glutamate, glycine and GABA(A) receptors, whereas inputs from the RdVII to jaw-opening motoneurons seem to be weak.

Unidirectional startle responses and disrupted left-right co-ordination of motor behaviors in robo3 mutant zebrafish.

The Roundabout (Robo) family of receptors and their Slit ligands play well-established roles in axonal guidance, including in humans where horizontal gaze palsy with progressive scoliosis (HGPPS) is caused by mutations in the robo3 gene. Although significant progress has been made toward understanding the mechanism by which Robo receptors establish commissural projections in the central nervous system, less is known about how these projections contribute to neural circuits mediating behavior. In this study, we report cloning of the zebrafish behavioral mutant twitch twice and show that twitch twice encodes robo3. We show that in mutant hindbrains the axons of an identified pair of neurons, the Mauthner cells, fail to cross the midline. The Mauthner neurons are essential for the startle response, and in twitch twice/robo3 mutants misguidance of the Mauthner axons results in a unidirectional startle response. Moreover, we show that twitch twice mutants exhibit normal visual acuity but display defects in horizontal eye movements, suggesting a specific and critical role for twitch twice/robo3 in sensory-guided behavior.

5-HT2A receptors are concentrated in regions of the human infant medulla involved in respiratory and autonomic control.

The serotonergic (5-HT) system in the human medulla oblongata is well-recognized to play an important role in the regulation of respiratory and autonomic function. In this study, using both immunocytochemistry (n=5) and tissue section autoradiography with the radioligand (125)I-1-(2,5-dimethoxy-4-iodo-phenyl)2-aminopropane (n=7), we examine the normative development and distribution of the 5-HT(2A) receptor in the human medulla during the last part of gestation and first postnatal year when dramatic changes are known to occur in respiratory and autonomic control, in part mediated by the 5-HT(2A) receptor. High 5-HT(2A) receptor binding was observed in the dorsal motor nucleus of the vagus (preganglionic parasympathetic output) and hypoglossal nucleus (airway patency); intermediate binding was present in the nucleus of the solitary tract (visceral sensory input), gigantocellularis, intermediate reticular zone, and paragigantocellularis lateralis. Negligible binding was present in the raphé obscurus and arcuate nucleus. The pattern of 5-HT(2A) immunoreactivity paralleled that of binding density. By 15 gestational weeks, the relative distribution of the 5-HT(2A) receptor was similar to that in infancy. In all nuclei sampled, 5-HT(2A) receptor binding increased with age, with significant increases in the hypoglossal nucleus (p=0.027), principal inferior olive (p=0.044), and medial accessory olive (0.038). Thus, 5-HT(2A) receptors are concentrated in regions involved in autonomic and respiratory control in the human infant medulla, and their developmental profile changes over the first year of life in the hypoglossal nucleus critical to airway patency and the inferior olivary complex essential to cerebellar function.

Development and organization of the descending serotonergic brainstem-spinal projections in the sea lamprey.

The organization and development of the descending spinal projections from serotonergic rhombencephalic neurons in the larval sea lamprey were investigated by double labeling, tract-tracing methods and immunocytochemistry against serotonin. The results showed that two serotonergic populations of the isthmic and vagal reticular regions present reticulospinal neurons from the beginning of the larval period. Of the three serotonergic subpopulations recognized in the isthmic reticular group [Abalo, X.M., Villar-Cheda, B., Meléndez-Ferro, M., Pérez-Costas, E., Anadón, R., Rodicio, M.C., 2007. Development of the serotonergic system in the central nervous system of the sea lamprey. J. Chem. Neuroanat. 34, 29-46], only two - the medial and ventral subpopulations - project to the spinal cord, with most of the projecting cells in the caudal part of the medial isthmic subpopulation. Occasional cells projecting to the spinal cord were observed in the ventral subpopulation. The vagal reticular serotonergic nucleus situated in the caudal rhombencephalon also presents cells with descending projections. The early development of the brainstem serotonergic projections to the spinal cord appears to be a conserved trait in all vertebrates studied. Although a serotonergic hindbrain-spinal projection system appears to have been present before the divergence of agnathans and gnathostomes, no serotonergic cells were observed in the raphe region in lamprey. Moreover, proportionally more rostral hindbrain serotonergic cells contribute to the spinal serotonergic projections in the sea lamprey than in jawed vertebrates.

Development of the vestibular apparatus and central vestibular connections in a wallaby (Macropus eugenii).

We have studied the early development of the vestibular apparatus and its central connections in the tammar wallaby (Macropus eugenii) in order to determine whether the vestibular system anatomy is sufficiently mature at birth to assist in climbing to the pouch. Structural development was studied with the aid of hematoxylin and eosin stained sections and immunoreactivity for GAP-43, whereas the development of vestibular system connections was examined by carbocyanine dye tracing. At the time of birth, the otocyst has distinct utricle, saccule and semicircular canals with immature sensory regions receiving innervation by GAP-43 immunoreactive fibers. Vestibular nerve fibers can be traced into the brainstem to the developing vestibular nuclei, which are not yet cytoarchitectonically distinct. The vestibular nuclei do not contribute direct projections to the lower cervical spinal cord at birth; most bulbospinal projections in the newborn appear to be derived bilaterally from the gigantocellular, lateral paragigantocellular reticular and ventral medullary nuclei. A substantial bilateral projection to the vestibular ganglion and apparatus from the region of the gigantocellular and lateral paragigantocellular nuclei was seen at birth, but not in subsequent ages. This is similar to a projection seen in newborn Ameridelphians. By postnatal day (P) 5, the vestibular apparatus had extensive projections to all vestibular nuclei and neurons projecting in the lateral vestibulospinal tract could be identified in the lateral vestibular nucleus. Cytoarchitectonic differentiation of the vestibular nuclei proceeded over the next 3 to 4 weeks with the emergence of discrete parvicellular and magnocellular components of the medial vestibular nucleus by P19. GAP-43 immunoreactivity stayed high in the lateral vestibulospinal tract for several months after birth, suggesting that the development of this tract followed a prolonged timecourse. Our findings indicate that central and peripheral connections of the vestibular ganglion are present at birth, but that there is no direct projection from the vestibular nuclei to the cervical spinal cord until P5. Nevertheless, the possibility remains that an indirect projection between the vestibular nuclei and the medial reticular formation is present at birth and mediates control of the climb.

Early defects of GABAergic synapses in the brain stem of a MeCP2 mouse model of Rett syndrome.

Rett syndrome is a neurodevelopmental disorder caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2) and represents the leading genetic cause for mental retardation in girls. MeCP2-mutant mice have been generated to study the molecular mechanisms of the disease. It was suggested that an imbalance between excitatory and inhibitory neurotransmission is responsible for the behavioral abnormalities, although it remained largely unclear which synaptic components are affected and how cellular impairments relate to the time course of the disease. Here, we report that MeCP2 KO mice present an imbalance between inhibitory and excitatory synaptic transmission in the ventrolateral medulla already at postnatal day 7. Focusing on the inhibitory synaptic transmission we show that GABAergic, but not glycinergic, synaptic transmission is strongly depressed in MeCP2 KO mice. These alterations are presumably due to both decreased presynaptic gamma-aminobutyric acid (GABA) release with reduced levels of the vesicular inhibitory transmitter transporter and reduced levels of postsynaptic GABA(A)-receptor subunits alpha2 and alpha4. Our data indicate that in the MeCP2 -/y mice specific synaptic molecules and signaling pathways are impaired in the brain stem during early postnatal development. These observations mandate the search for more refined diagnostic tools and may provide a rationale for the timing of future therapeutic interventions in Rett patients.

Interaction between hindbrain and spinal networks during the development of locomotion in zebrafish.

Little is known about the role of the hindbrain during development of spinal network activity. We set out to identify the activity patterns of reticulospinal (RS) neurons of the hindbrain in fictively swimming (paralyzed) zebrafish larvae. Simultaneous recordings of RS neurons and spinal motoneurons revealed that these were coactive during spontaneous fictive swim episodes. We characterized four types of RS activity patterns during fictive swimming: (i) a spontaneous pattern of discharges resembling evoked high-frequency spiking during startle responses to touch stimuli, (ii) a rhythmic pattern of excitatory postsynaptic potentials (EPSPs) whose frequency was similar to the motoneuron EPSP frequency during swim episodes, (iii) an arrhythmic pattern consisting of tonic firing throughout swim episodes, and (iv) RS cell activity uncorrelated with motoneuron activity. Despite lesions to the rostral spinal cord that prevented ascending spinal axons from entering the hindbrain (normally starting at approximately 20 h), RS neurons continued to display the aforementioned activity patterns at day 3. However, removal of the caudal portion of the hindbrain prior to the descent of RS axons left the spinal cord network unable to generate the rhythmic oscillations normally elicited by application of N-methyl-d-aspartate (NMDA), but in approximately 40% of cases chronic incubation in NMDA maintained rhythmic activity. We conclude that there is an autonomous embryonic hindbrain network that is necessary for proper development of the spinal central pattern generator, and that the hindbrain network can partially develop independently of ascending input.

GABAergic modulation of developing pedunculopontine nucleus.

Rapid eye movement sleep decreases dramatically during development. We tested the hypothesis that some of this decrease may be due to GABAergic inhibition of reticular activating system neurons. Recordings of pedunculopontine neurons in vitro showed that the gamma-amino-butyric acid, receptor agonist muscimol depolarized noncholinergic cells early in the developmental decrease in rapid eye movement sleep, and hyperpolarized them later. Most cholinergic cells were hyperpolarized throughout the period tested. The gamma-amino-butyric acid b receptor agonist baclofen hyperpolarized both cholinergic and noncholinergic cells, although the degree of polarization decreased with age. Part of the gradual decrement in rapid eye movement sleep during development may be due in part to the increasing inhibition mediated by gamma-amino-butyric acid, a receptor on pedunculopontine neurons. This influence, however, appears to be mainly on noncholinergic cells.

Serotonergic reticular formation cells in Rana pipiens: categorization, development, and tectal projections.

The reticular formation contributes serotonin to many brain regions, including the optic tectum. We examined the organization and development of its serotonergic neurons in the leopard frog. Serotonin-immunoreactive (5-HT-ir) cells in adult frogs were organized into 10 distinct populations that were identified on the basis of their location and cellular morphology. Populations ranged in size from 16 to 2,066 cells and sometimes spanned more than one previously identified nuclear region. Four of the ten populations were absent in tadpoles. The remaining populations, though present, had two contrasting patterns of development. Half of the populations were established early and showed little change in numbers during tadpole stages but increased in size in juvenile and adult frogs. The other half increased dramatically during tadpole stages but failed to add many more cells in juveniles and adults. Three populations provided 90% of the serotonergic projections from the reticular region to the adult optic tectum. These projections were established early in development and likely originated from the dorsal raphe, median raphe, raphe pontis, raphe magnus, and reticularis pontis oralis. Termination sites were located in midtectal layers and were not topographically organized. We conclude that serotonergic cells within the reticular formation of the leopard frog have an organization similar to that found in mammals, that the overall increase in numbers of these cells is attributable to growth in different cell populations at different stages, and that input from this region changes activity levels in the optic tectum in a global rather than a site-specific manner.

The ontogeny of Krox-20 expression in brainstem and cerebellar neurons.

The central expression of Krox-20, a C(2)H(2)-type zinc-finger transcription factor and immediate early gene, is primarily studied in the young embryo, where it contributes to rhombomere (r) r3 and r5 development. Data regarding the cellular localization and developmental regulation of Krox-20 protein expression in brainstem neurons are lacking. Our interest in brainstem development, coupled with findings from our lab and others that demonstrate a profound impact of a Krox-20 null mutation on brainstem-mediated behaviors, led us to investigate the spatiotemporal expression of Krox-20 protein in brainstem and cerebellar neurons to gain insight into potential cellular targets of the mutation. Understanding the cellular localization of Krox-20 is important in light of studies showing the impact of immediate early gene expression on neuronal function. Krox-20 immunohistochemistry experiments were conducted on animals at embryonic days (E) 17.0 and 18.5 and postnatal days (P) 0-1, 3-4, 7, 14, 22, and adulthood. Krox-20 expression is developmentally regulated in motoneurons, somatosensory-related neurons, Purkinje cells, and components of auditory circuitry. Neurons in the ventral cochlear nucleus and inferior colliculus show a sustained Krox-20 expression. Ultrastructural data demonstrate Krox-20 expression in somata and dendrites of central neurons. Our identification of Krox-20 expressing neurons provides us a better understanding of the behavioral consequences of the mutation. Furthermore, our results suggest that Krox-20 protein has a role in the maturation of particular brainstem and cerebellar neurons and fluctuations in Krox-20 protein expression coincide with the development of circuitry underlying brainstem-mediated behaviors.

Disturbance of phasic chin muscle activity during rapid-eye-movement sleep.

In patients with Rett syndrome (RS), a peculiar type of disturbance in phasic chin muscle activity during rapid-eye-movement sleep (REMS) (e.g. an elevation of phasic inhibition index (PII) without an affection of tonic inhibition index (TII)) has been reported. The similar disturbance in REMS was reported not only in child patients with infantile spasms, severe myoclonic epilepsy in infancy (SMEI), severe nocturnal enuresis, and autism but also in adult patients with Parkinson's disease (PD). Except for SMEI and PD, patients with the other four clinical entities including RS could express autistic tendency. Since the responsible lesion for the occurrence of an elevation of PII with a normal TII value is likely to be in the pontine tegmentum, this subcortical structure is hypothesized to be involved in the appearance of autistic tendency.

[Synapse architectonics of the cerebral cortex in the evolutionary aspect]. / Sinapsoarkhitektonika kory bol'shogo mozga v évoliutsionnom aspekte.

The formation of synapses in ontogenesis is an important problem of neuromorphology. The paper shows that the bulk of synapses of the developing brain is formed on the basis of previous specialization of membranes. Early in ontogenesis, most formed synapses shows asymmetric contacts. In postnatal ontogenesis, the formation of synapses proceeds due to the simultaneous occurrence of specialization of membranes and synaptic vesicles, by forming a "dot" active zone. Systemogenesis, such as the general law of brain development, plays an important role in understanding the functional significance of the shown mechanisms of maturation of synapses.

Nucleus-specific differences in GABA(A)-receptor-mediated inhibition are enhanced during thalamic development.

Inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors are much slower in neurons of the thalamic reticular nucleus (RTN) versus those in the ventrobasal complex (VB) of young rats. Here we confirm and extend those findings regarding GABA(A) response heterogeneity especially in relation to development. Whole cell patch-clamp recordings were used to investigate GABA(A) spontaneous and electrically evoked IPSCs (sIPSCs/eIPSCs) in RTN and VB cells of different aged rats. Consistent with earlier findings, sIPSC duration at P8-12 was considerably longer in RTN (weighted decay time constant: tau(D,W) = 56.2 +/- 4.9 ms; mean +/- SE) than in VB (tau(D,W) = 15.8 +/- 1.0 ms) neurons. Decay kinetics in RTN neurons did not differ at P21-30 (45.5 +/- 4.7 ms) or P42-60 (51.6 +/- 10.6 ms). In contrast, VB sIPSCs were significantly faster at both P21-30 (tau(D,W) = 10.8 +/- 0.9 ms) and P42-60 (tau(D,W) = 9.2 +/- 0.4 ms) compared with P8-12 animals. IPSCs displayed differential outward rectification and temperature dependence, providing further support for nucleus-specific responses. tau(D,W) increased with membrane depolarization but with a net larger effect in VB. By contrast, tau(D,W) was always smaller at higher temperatures but with relatively greater difference observed in RTN. Thus nuclear differences in GABA(A) IPSCs are not only maintained, but enhanced in the mature rodent under physiological conditions. These findings support our hypothesis that unique GABA(A) receptors mediate slowly decaying RTN IPSCs that are a critical and enduring feature of the thalamic circuit. This promotes powerful intranuclear inhibition and likely prevents epileptiform thalamocortical hypersynchrony.

Regeneration of supraspinal axons after transection of the thoracic spinal cord in the developing opossum, Didelphis virginiana.

When the thoracic spinal cord of the North American opossum is transected early in development, supraspinal axons grow through the lesion. In the experiments reported here, we asked whether regeneration of cut axons contributes to such growth. Fast Blue (FB) was injected into the lumbar cord on postnatal day (PD)5, 8, 15, or 20. Five days later, FB was removed by gentle suction, and the spinal cord was transected at thoracic levels. Fourteen days later, rhodamine B dextran was injected between the site of the FB injection and the lesion. The pups were maintained for an additional 7-10 days before killing and perfusion. We assumed that supraspinal neurons that contained FB survived axotomy and those that contained both FB and rhodamine B dextran supported regenerating axons. In the PD5 group (lesioned at PD10), regenerative growth was documented for axons originating in all of the supraspinal nuclei that innervate the lumbar cord by PD10. When the injections were made at the later ages, however, neurons that supported regenerative growth were fewer in number and regionally restricted. In some cases, they were limited primarily to the red nucleus, the medullary raphe, and the adjacent reticular formation. Our results show that regeneration of cut axons contributes to growth of supraspinal axons through the lesion after transection of the thoracic cord in developing opossums and that the critical period for regenerative growth is not the same for all axons.

Changes in Fos-like immunoreactivity evoked by maturation of the sneeze reflex triggered by nasal air puff stimulation in kittens.

The sneeze reflex is a valuable tool for exploring the maturation of the respiratory control in the newborn as it alters both inspiratory and expiratory activities. Air puff stimulation of the superior nasal meatus innervated by ethmoidal afferents consistently evokes sneeze in adult cats. Such stimulation evokes only a reinforcement of expiratory activities in newborn kittens. This study demonstrates that the pattern of Fos-like immunoreactivity evoked by nasal stimulation changes during functional maturation of sneeze. Nasal stimulation evoked immunoreactivity (i) in the trigeminal sensory complex, at the levels where nasal afferents project, (ii) in the reticular formation, (iii) in the solitary complex and (iv) in the parabrachial area of mature kittens. The evoked immunoreactivity was the same in newborn kittens as in mature kittens in the projection areas of the nasal primary afferents. Fos response was less than half that in mature kittens in the reticular formation and absent in the solitary complex or the parabrachial area. Sneeze can be elicited from the time when evoked immunoreactivity in the solitary complex and the parabrachial area is above control levels. These data provide evidence that the maturation of sneeze is dependent on the development of central relays allowing peripheral inputs to be integrated by neurons engaged in respiratory control.