Projections from the paralemniscal nucleus to the spinal cord in the mouse

The present study investigated the projection from the paralemniscal nucleus (PL) to the spinal cord in the mouse by injecting the retrograde tracer fluoro-gold to different levels of the spinal cord and injecting the anterograde tracer biotinylated dextran amine into PL. We found that PL projects to the entire spinal cord with obvious contralateral predominance—420 neurons projected to the contralateral cervical cord and 270 to the contralateral lumbar cord. Fibers from PL descended in the dorsolateral funiculus on the contralateral side and terminated in laminae 5, 6, 7, and to a lesser extent in the dorsal and ventral horns. A smaller number of fibers also descended in the ventral funiculus on the ipsilateral side and terminated in laminae 7, 8 and, to a lesser extent in lamina 9. The present study is the first demonstration of the PL fiber termination in the spinal cord in mammals. The PL projection to the spinal cord may be involved in vocalization and locomotion

Ventilatory Chaos Is Impaired in Carotid Atherosclerosis

Ventilatory chaos is strongly linked to the activity of central pattern generators, alone or influenced by respiratory or cardiovascular afferents. We hypothesized that carotid atherosclerosis should alter ventilatory chaos through baroreflex and autonomic nervous system dysfunctions. Chaotic dynamics of inspiratory flow was prospectively evaluated in 75 subjects undergoing carotid ultrasonography: 27 with severe carotid stenosis (>70%), 23 with moderate stenosis (<70%), and 25 controls. Chaos was characterized by the noise titration method, the correlation dimension and the largest Lyapunov exponent. Baroreflex sensitivity was estimated in the frequency domain. In the control group, 92% of the time series exhibit nonlinear deterministic chaos with positive noise limit, whereas only 68% had a positive noise limit value in the stenoses groups. Ventilatory chaos was impaired in the groups with carotid stenoses, with significant parallel decrease in the noise limit value, correlation dimension and largest Lyapunov exponent, as compared to controls. In multiple regression models, the percentage of carotid stenosis was the best in predicting the correlation dimension (p<0.001, adjusted R2: 0.35) and largest Lyapunov exponent (p<0.001, adjusted R2: 0.6). Baroreflex sensitivity also predicted the correlation dimension values (p = 0.05), and the LLE (p = 0.08). Plaque removal after carotid surgery reversed the loss of ventilatory complexity. To conclude, ventilatory chaos is impaired in carotid atherosclerosis. These findings depend on the severity of the stenosis, its localization, plaque surface and morphology features, and is independently associated with baroreflex sensitivity reduction. These findings should help to understand the determinants of ventilatory complexity and breathing control in pathological conditions

Nociceptive Afferents to the Premotor Neurons That Send Axons Simultaneously to the Facial and Hypoglossal Motoneurons by Means of Axon Collaterals

It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR) responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG) or FG/tetramethylrhodamine-dextran amine (TMR-DA) were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the caudal spinal trigeminal nucleus (Vc). The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt), dorsal and ventral medullary reticular formation (MdD, MdV), supratrigeminal nucleus (Vsup) and parabrachial nucleus (PBN) with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP) was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals

Cues for Early Social Skills: Direct Gaze Modulates Newborns' Recognition of Talking Faces

Previous studies showed that, from birth, speech and eye gaze are two important cues in guiding early face processing and social cognition. These studies tested the role of each cue independently; however, infants normally perceive speech and eye gaze together. Using a familiarization-test procedure, we first familiarized newborn infants (n = 24) with videos of unfamiliar talking faces with either direct gaze or averted gaze. Newborns were then tested with photographs of the previously seen face and of a new one. The newborns looked longer at the face that previously talked to them, but only in the direct gaze condition. These results highlight the importance of both speech and eye gaze as socio-communicative cues by which infants identify others. They suggest that gaze and infant-directed speech, experienced together, are powerful cues for the development of early social skills

The Neurotoxicity of DOPAL: Behavioral and Stereological Evidence for Its Role in Parkinson Disease Pathogenesis

BACKGROUND: The etiology of Parkinson disease (PD) has yet to be fully elucidated. We examined the consequences of injections of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a toxic metabolite of dopamine, into the substantia nigra of rats on motor behavior and neuronal survival. METHODS/PRINCIPAL FINDINGS: A total of 800 nl/rat of DOPAL (1 µg/200 nl) was injected stereotaxically into the substantia nigra over three sites while control animals received similar injections of phosphate buffered saline. Rotational behavior of these rats was analyzed, optical density of striatal tyrosine hydroxylase was calculated, and unbiased stereological counts of the substantia nigra were made. The rats showed significant rotational asymmetry ipsilateral to the lesion, supporting disruption of dopaminergic nigrostriatal projections. Such disruption was verified since the density of striatal tyrosine hydroxylase decreased significantly (p<0.001) on the side ipsilateral to the DOPAL injections when compared to the non-injected side. Stereological counts of neurons stained for Nissl in pars compacta of the substantia nigra significantly decreased (p<0.001) from control values, while counts of those in pars reticulata were unchanged after DOPAL injections. Counts of neurons immunostained for tyrosine hydroxylase also showed a significant (p=0.032) loss of dopaminergic neurons. In spite of significant loss of dopaminergic neurons, DOPAL injections did not induce significant glial reaction in the substantia nigra. CONCLUSIONS: The present study provides the first in vivo quantification of substantia nigra pars compacta neuronal loss after injection of the endogenous toxin DOPAL. The results demonstrate that injections of DOPAL selectively kills SN DA neurons, suggests loss of striatal DA terminals, spares non-dopaminergic neurons of the pars reticulata, and triggers a behavioral phenotype (rotational asymmetry) consistent with other PD animal models. This study supports the "catecholaldehyde hypothesis" as an important link for the etiology of sporadic PD

Cardiorespiratory and neural consequences of rats brought past their aerobic dive limit

The mammalian diving response is a dramatic autonomic adjustment to underwater submersion affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is known to be modulated by the parasympathetic nervous system, arterial blood pressure is modulated via the sympathetic system, and still other circuits modulate the respiratory changes. In the present study, we investigate the submergence of rats brought past their aerobic dive limit, defined as the diving duration beyond which blood lactate concentration increases above resting levels. Hemodynamic measurements were made during underwater submergence with biotelemetric transmitters, and blood was drawn from cannulas previously implanted in the rats' carotid arteries. Such prolonged submersion induces radical changes in blood chemistry; mean arterial Pco2 rose to 62.4 Torr, while mean arterial Po2 and pH reached nadirs of 21.8 Torr and 7.18, respectively. Despite these radical changes in blood chemistry, the rats neither attempted to gasp nor breathe while underwater. Immunohistochemistry for Fos protein done on their brains revealed numerous Fos-positive profiles. Especially noteworthy were the large number of immunopositive profiles in loci where presumptive chemoreceptors are found. Despite the activation of these presumptive chemoreceptors, the rats did not attempt to breathe. Injections of biotinylated dextran amine were made into ventral parts of the medullary dorsal horn, where central fibers of the anterior ethmoidal nerve terminate. Labeled fibers coursed caudal, ventral, and medial from the injection to neurons on the ventral surface of the medulla, where numerous Fos-labeled profiles were seen in the rats brought past their aerobic dive limit. We propose that this projection inhibits the homeostatic chemoreceptor reflex, despite the gross activation of chemoreceptors

The rat: a laboratory model for studies of the diving response

Underwater submersion in mammals induces apnea, parasympathetically mediated bradycardia, and sympathetically mediated peripheral vasoconstriction. These effects are collectively termed the diving response, potentially the most powerful autonomic reflex known. Although these physiological responses are directed by neurons in the brain, study of neural control of the diving response has been hampered since 1) it is difficult to study the brains of animals while they are underwater, 2) feral marine mammals are usually large and have brains of variable size, and 3) there are but few references on the brains of naturally diving species. Similar responses are elicited in anesthetized rodents after stimulation of their nasal mucosa, but this nasopharyngeal reflex has not been compared directly with natural diving behavior in the rat. In the present study, we compared hemodynamic responses elicited in awake rats during volitional underwater submersion with those of rats swimming on the water's surface, rats involuntarily submerged, and rats either anesthetized or decerebrate and stimulated nasally with ammonia vapors. We show that the hemodynamic changes to voluntary diving in the rat are similar to those of naturally diving marine mammals. We also show that the responses of voluntary diving rats are 1) significantly different from those seen during swimming, 2) generally similar to those elicited in trained rats involuntarily “dunked” underwater, and 3) generally different from those seen from dunking naive rats underwater. Nasal stimulation of anesthetized rats differed most from the hemodynamic variables of rats trained to dive voluntarily. We propose that the rat trained to dive underwater is an excellent laboratory model to study neural control of the mammalian diving response, and also suggest that some investigations may be done with nasal stimulation of decerebrate preparations to decipher such control