RESUMEN
Somatosensation is essential for animals to perceive the external world through touch, allowing them to detect physical contact, temperature, pain, and body position. Studies on rodent vibrissae have highlighted the organization and processing in mammalian somatosensory pathways.1,2 Comparative research across vertebrates is vital for understanding evolutionary influences and ecological specialization on somatosensory systems. Birds, with their diverse morphologies, sensory abilities, and behaviors, serve as ideal models for investigating the evolution of somatosensation. Prior studies have uncovered tactile-responsive areas within the avian telencephalon, particularly in pigeons,3,4,5,6 parrots,7 and finches,8 but variations in somatosensory maps and responses across avian species are not fully understood. This study aims to explore somatotopic organization and neural coding in the telencephalon of Anna's hummingbirds (Calypte anna) and zebra finches (Taeniopygia guttata) by using in vivo extracellular electrophysiology to record activity in response to controlled tactile stimuli on various body regions. These findings reveal unique representations of body regions across distinct forebrain somatosensory nuclei, indicating significant differences in the extent of areas dedicated to certain body surfaces, which may correlate with their behavioral importance.
Asunto(s)
Pinzones , Prosencéfalo , Animales , Pinzones/fisiología , Prosencéfalo/fisiología , Tacto/fisiología , Aves/fisiología , Masculino , Percepción del Tacto/fisiología , FemeninoRESUMEN
Birds have a comprehensive network of sensorimotor projections extending from the forebrain and midbrain to the cerebellum via the pontine nuclei, but the organization of these circuits in the pons is not thoroughly described. Inputs to the pontine nuclei include two retinorecipient areas, nucleus lentiformis mesencephali (LM) and nucleus of the basal optic root (nBOR), which are important structures for analyzing optic flow. Other crucial regions for visuomotor control include the retinorecipient ventral lateral geniculate nucleus (GLv), and optic tectum (TeO). These visual areas, together with the somatosensory area of the anterior (rostral) Wulst, which is homologous to the primary somatosensory cortex in mammals, project to the medial and lateral pontine nuclei (PM, PL). In this study, we used injections of fluorescent tracers to study the organization of these visual and somatosensory inputs to the pontine nuclei in zebra finches. We found a topographic organization of inputs to PM and PL. The PM has a lateral subdivision that predominantly receives projections from the ipsilateral anterior Wulst. The medial PM receives bands of inputs from the ipsilateral GLv and the nucleus laminaris precommisulis, located medial to LM. We also found that the lateral PL receives a strong ipsilateral projection from TeO, while the medial PL and region between the PM and PL receive less prominent projections from nBOR, bilaterally. We discuss these results in the context of the organization of pontine inputs to the cerebellum and possible functional implications of diverse somato-motor and visuomotor inputs and parcellation in the pontine nuclei.
Asunto(s)
Pinzones , Vías Visuales , Animales , Colículos Superiores , Puente , Cerebelo , MamíferosRESUMEN
In birds, the nucleus of the basal optic root (nBOR) and the nucleus lentiformis mesencephali (LM) are brainstem nuclei involved in the analysis of optic flow. A major projection site of both nBOR and LM is the medial column of the inferior olive (IO), which provides climbing fibers to the vestibulocerebellum. This pathway has been well documented in pigeons, but not other birds. Recent works have highlighted that zebra finches show specializations with respect to optic flow processing, which may be reflected in the organization of optic flow pathways to the IO. In this study, we characterized the organization of these pathways in zebra finches. We found that the medial column consists of at least eight subnuclei (i-viii) visible in Nissl-stained tissue. Using anterograde traces we found that the projections from LM and nBOR to the IO were bilateral, but heavier to the ipsilateral side, and showed a complementary pattern: LM projected to subnucleus i, whereas nBOR projected to subnuclei ii and v. Using retrograde tracers, we found that these subnuclei (i, ii and v) projected to the vestibulocerebellum (folia IXcd and X), whereas the other subnuclei projected to IXab and the lateral margin of VII and VIII. The nBOR also projected ipsilaterally to the caudo-medial dorsal lamella of the IO, which the retrograde experiments showed as projecting to the medial margin of VII and VIII. We compare these results with previous studies in other avian species.
Asunto(s)
Pinzones , Flujo Optico , Animales , Vías Visuales , Columbidae , Cerebelo , Núcleo OlivarRESUMEN
Hummingbirds possess distinct metabolic adaptations to fuel their energy-demanding hovering flight, but the underlying genomic changes are largely unknown. Here, we generated a chromosome-level genome assembly of the long-tailed hermit and screened for genes that have been specifically inactivated in the ancestral hummingbird lineage. We discovered that FBP2 (fructose-bisphosphatase 2), which encodes a gluconeogenic muscle enzyme, was lost during a time period when hovering flight evolved. We show that FBP2 knockdown in an avian muscle cell line up-regulates glycolysis and enhances mitochondrial respiration, coincident with an increased mitochondria number. Furthermore, genes involved in mitochondrial respiration and organization have up-regulated expression in hummingbird flight muscle. Together, these results suggest that FBP2 loss was likely a key step in the evolution of metabolic muscle adaptations required for true hovering flight.
Asunto(s)
Adaptación Fisiológica , Aves , Vuelo Animal , Fructosa-Bifosfatasa , Gluconeogénesis , Músculo Esquelético , Animales , Aves/genética , Aves/metabolismo , Metabolismo Energético/genética , Vuelo Animal/fisiología , Gluconeogénesis/genética , Adaptación Fisiológica/genética , Fructosa-Bifosfatasa/genética , Músculo Esquelético/enzimologíaRESUMEN
All visual animals experience optic flow-global visual motion across the retina, which is used to control posture and movement.1 The midbrain circuitry for optic flow is highly conserved in vertebrates,2-6 and these neurons show similar response properties across tetrapods.4,7-16 These neurons have large receptive fields and exhibit both direction and velocity selectivity in response to large moving stimuli. Hummingbirds deviate from the typical vertebrate pattern in several respects.17,18 Their lentiformis mesencephali (LM) lacks the directional bias seen in other tetrapods and has an overall bias for faster velocities. This led Ibbotson19 to suggest that the hummingbird LM may be specialized for hovering close to visual structures, such as plants. In such an environment, even slight body motions will translate into high-velocity optic flow. A prediction from this hypothesis is that hummingbird LM neurons should be more responsive to large visual features. We tested this hypothesis by measuring neural responses of hummingbirds and zebra finches to sine wave gratings of varying spatial and temporal frequencies. As predicted, the hummingbird LM displayed an overall preference for fast optic flow because neurons were biased to lower spatial frequencies. These neurons were also tightly tuned in the spatiotemporal domain. We found that the zebra finch LM specializes along another domain: many neurons were initially tuned to high temporal frequencies followed by a shift in location and orientation to slower velocity tuning. Collectively, these results demonstrate that the LM has distinct and specialized tuning properties in at least two bird species.
Asunto(s)
Pinzones , Percepción de Movimiento , Flujo Optico , Área Pretectal , Animales , Movimiento (Física) , Percepción de Movimiento/fisiología , Neuronas/fisiología , Estimulación Luminosa/métodos , Vías Visuales/fisiologíaRESUMEN
Optokinetic responses function to maintain retinal image stabilization by minimizing optic flow that occurs during self-motion. The hovering ability of hummingbirds is an extreme example of this behavior. Optokinetic responses are mediated by direction-selective neurons with large receptive fields in the accessory optic system (AOS) and pretectum. Recent studies in hummingbirds showed that, compared with other bird species, 1) the pretectal nucleus lentiformis mesencephali (LM) is hypertrophied, 2) LM has a unique distribution of direction preferences, and 3) LM neurons are more tightly tuned to stimulus velocity. In this study, we sought to determine if there are concomitant changes in the nucleus of the basal optic root (nBOR) of the AOS. We recorded the visual response properties of nBOR neurons to large-field-drifting random dot patterns and sine-wave gratings in Anna's hummingbirds and zebra finches and compared these with archival data from pigeons. We found no differences with respect to the distribution of direction preferences: Neurons responsive to upward, downward, and nasal-to-temporal motion were equally represented in all three species, and neurons responsive to temporal-to-nasal motion were rare or absent (<5%). Compared with zebra finches and pigeons, however, hummingbird nBOR neurons were more tightly tuned to stimulus velocity of random dot stimuli. Moreover, in response to drifting gratings, hummingbird nBOR neurons are more tightly tuned in the spatiotemporal domain. These results, in combination with specialization in LM, support a hypothesis that hummingbirds have evolved to be "optic flow specialists" to cope with the optomotor demands of sustained hovering flight.NEW & NOTEWORTHY Hummingbirds have specialized response properties to optic flow in the pretectal nucleus lentiformis mesencephali (LM). The LM works with the nucleus of the basal optic root (nBOR) of the accessory optic system (AOS) to process global visual motion, but whether the neural response specializations observed in the LM extend to the nBOR is unknown. Hummingbird nBOR neurons are more tightly tuned to visual stimulus velocity, and in the spatiotemporal domain, compared with two nonhovering species.
Asunto(s)
Aves/fisiología , Mesencéfalo/fisiología , Percepción de Movimiento/fisiología , Neuronas/fisiología , Flujo Optico/fisiología , Reconocimiento Visual de Modelos/fisiología , Animales , Conducta Animal/fisiología , Columbidae/fisiología , Pinzones/fisiología , Técnicas de Placa-Clamp , Área Pretectal/fisiología , Especificidad de la EspecieRESUMEN
In birds, optic flow is processed by a retinal-recipient nucleus in the pretectum, the nucleus lentiformis mesencephali (LM), which then projects to the cerebellum, a key site for sensorimotor integration. Previous studies have shown that the LM is hypertrophied in hummingbirds, and that LM cell response properties differ between hummingbirds and other birds. Given these differences in anatomy and physiology, we ask here if there are also species differences in the connectivity of the LM. The LM is separated into lateral and medial subdivisions, which project to the oculomotor cerebellum and the vestibulocerebellum. In pigeons, the projection to the vestibulocerebellum largely arises from the lateral LM; the projection to the oculomotor cerebellum largely arises from the medial LM. Here, using retrograde tracing, we demonstrate differences in the distribution of projections in these pathways between Anna's hummingbirds (Calypte anna), zebra finches (Taeniopygia guttata), and pigeons (Columba livia). In all three species, the projections to the vestibulocerebellum were largely from lateral LM. In contrast, projections to the oculomotor cerebellum in hummingbirds and zebra finches do not originate in the medial LM (as in pigeons) but instead largely arise from pretectal structures just medial, the nucleus laminaris precommissuralis and nucleus principalis precommissuralis. These species differences in projection patterns provide further evidence that optic flow circuits differ among bird species with distinct modes of flight.
Asunto(s)
Aves/anatomía & histología , Cerebelo/anatomía & histología , Área Pretectal/anatomía & histología , Animales , Vías Eferentes/anatomía & histología , Inmunohistoquímica , Masculino , Microscopía Fluorescente , Técnicas de Trazados de Vías Neuroanatómicas , Vías Visuales/anatomía & histologíaRESUMEN
In this paper, we review the connections and physiology of visual pathways to the cerebellum in birds and consider their role in flight. We emphasize that there are two visual pathways to the cerebellum. One is to the vestibulocerebellum (folia IXcd and X) that originates from two retinal-recipient nuclei that process optic flow: the nucleus of the basal optic root (nBOR) and the pretectal nucleus lentiformis mesencephali (LM). The second is to the oculomotor cerebellum (folia VI-VIII), which receives optic flow information, mainly from LM, but also local visual motion information from the optic tectum, and other visual information from the ventral lateral geniculate nucleus (Glv). The tectum, LM and Glv are all intimately connected with the pontine nuclei, which also project to the oculomotor cerebellum. We believe this rich integration of visual information in the cerebellum is important for analyzing motion parallax that occurs during flight. Finally, we extend upon a suggestion by Ibbotson (2017) that the hypertrophy that is observed in LM in hummingbirds might be due to an increase in the processing demands associated with the pathway to the oculomotor cerebellum as they fly through a cluttered environment while feeding.
RESUMEN
In birds, the nucleus of the basal optic root (nBOR) and the nucleus lentiformis mesencephali (LM) are retinal recipient nuclei involved in the analysis of optic flow and the generation of the optokinetic response. In both pigeons and chickens, retinal inputs to the nBOR arise from displaced ganglion cells (DGCs), which are found at the margin of the inner nuclear and inner plexiform layers. The LM receives afferents from retinal ganglion cells, but whether DGCs also project to LM is a matter of debate. Previous work in chickens had concluded that DGCs do not project to LM, but a recent study in pigeons found that both retinal ganglion cells and DGCs project to LM. These findings leave open the question of whether there are species differences with respect to the DGC projection to LM. In the present study, we made small injections of retrograde tracer into the LM in a zebra finch and an Anna's hummingbird. In both cases, retrogradely labeled retinal ganglion cells and DGCs were observed. These results suggest that a retinal input to the LM arising from DGCs is characteristic of most, if not all, birds.
Asunto(s)
Aves/anatomía & histología , Aves/fisiología , Cuerpo Estriado/anatomía & histología , Cuerpo Estriado/fisiología , Retina/anatomía & histología , Retina/fisiología , Animales , Masculino , Técnicas de Trazados de Vías Neuroanatómicas , Neuronas/citología , Neuronas/fisiología , Vías Visuales/anatomía & histología , Vías Visuales/fisiología , Percepción Visual/fisiologíaRESUMEN
Neurons in animal visual systems that respond to global optic flow exhibit selectivity for motion direction and/or velocity. The avian lentiformis mesencephali (LM), known in mammals as the nucleus of the optic tract (NOT), is a key nucleus for global motion processing [1-4]. In all animals tested, it has been found that the majority of LM and NOT neurons are tuned to temporo-nasal (back-to-front) motion [4-11]. Moreover, the monocular gain of the optokinetic response is higher in this direction, compared to naso-temporal (front-to-back) motion [12, 13]. Hummingbirds are sensitive to small visual perturbations while hovering, and they drift to compensate for optic flow in all directions [14]. Interestingly, the LM, but not other visual nuclei, is hypertrophied in hummingbirds relative to other birds [15], which suggests enhanced perception of global visual motion. Using extracellular recording techniques, we found that there is a uniform distribution of preferred directions in the LM in Anna's hummingbirds, whereas zebra finch and pigeon LM populations, as in other tetrapods, show a strong bias toward temporo-nasal motion. Furthermore, LM and NOT neurons are generally classified as tuned to "fast" or "slow" motion [10, 16, 17], and we predicted that most neurons would be tuned to slow visual motion as an adaptation for slow hovering. However, we found the opposite result: most hummingbird LM neurons are tuned to fast pattern velocities, compared to zebra finches and pigeons. Collectively, these results suggest a role in rapid responses during hovering, as well as in velocity control and collision avoidance during forward flight of hummingbirds.
Asunto(s)
Vuelo Animal/fisiología , Neuronas/fisiología , Pájaros Cantores/fisiología , Vías Visuales , Animales , Percepción de Movimiento , Neuronas/citología , Estimulación LuminosaRESUMEN
Birds are almost always said to have two visual pathways from the retina to the telencephalon: thalamofugal terminating in the Wulst, and tectofugal terminating in the entopallium. Often ignored is a second tectofugal pathway that terminates in the nidopallium medial to and separate from the entopallium (e.g., Gamlin and Cohen [1986] J Comp Neurol 250:296-310). Using standard tract-tracing and electroanatomical techniques, we extend earlier evidence of a second tectofugal pathway in songbirds (Wild [1994] J Comp Neurol 349:512-535), by showing that visual projections to nucleus uvaeformis (Uva) of the posterior thalamus in zebra finches extend farther rostrally than to Uva, as generally recognized in the context of the song control system. Projections to "rUva" resulted from injections of biotinylated dextran amine into the lateral pontine nucleus (PL), and led to extensive retrograde labeling of tectal neurons, predominantly in layer 13. Injections in rUva also resulted in extensive retrograde labeling of predominantly layer 13 tectal neurons, retrograde labeling of PL neurons, and anterograde labeling of PL. It thus appears that some tectal neurons could project to rUva and PL via branched axons. Ascending projections of rUva terminated throughout a visually responsive region of the intermediate nidopallium (NI) lying between the nucleus interface medially and the entopallium laterally. Lastly, as shown by Clarke in pigeons ([1977] J Comp Neurol 174:535-552), we found that PL projects to caudal cerebellar folia.
Asunto(s)
Pinzones/fisiología , Tegmento Pontino/fisiología , Núcleos Talámicos Posteriores/fisiología , Techo del Mesencéfalo/fisiología , Estimulación Acústica/métodos , Animales , Femenino , Pinzones/anatomía & histología , Masculino , Estimulación Luminosa/métodos , Tegmento Pontino/citología , Núcleos Talámicos Posteriores/citología , Pájaros Cantores , Techo del Mesencéfalo/citología , Vías Visuales/citologíaRESUMEN
This study focuses on presympathetic neurons of the rostral ventrolateral medulla (RVLM) that regulate sympathetic vasomotor tone. Many neurotransmitters are colocalized in RVLM neurons and are released under specific conditions to modulate efferent homeostatic responses. Of particular interest here are two peptides colocalized in catecholaminergic RVLM neurons: catestatin and pituitary adenylate cyclase-activating polypeptide (PACAP). Chromogranin A-derived catestatin is a potent endogenous noncompetitive nicotinic and adrenoreceptor antagonist. Catestatin impairs adenylate cyclase and phospholipase C action: mechanisms engaged by PACAP. Although PACAP and catestatin are likely coreleased, the possible effects of this are unknown. We aimed to determine whether catestatin affects the normal sympathoexcitatory but isotensive responses to intrathecal PACAP. Urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats (n = 22) were given an intrathecal injection of catestatin at different times prior to intrathecal administration of PACAP-38. Arterial pressure, splanchnic sympathetic nerve activity, heart rate, and reflex responses to baroreceptor and chemoreceptor activation were recorded. The key findings of this study are that pretreatment with catestatin time dependently enhances the PACAP-38 effect on mean arterial pressure and enhances sympathetic barosensitivity and chemosensitivity. The time-scale of the effect of catestatin on the response to PACAP-38 strongly suggests that catestatin is either causing changes in gene expression to exert its effects, or modifying intracellular mechanisms normally engaged by PAC(1) receptors. The ability of catestatin pretreatment to enhance barosensitivity and chemosensitivity after PACAP-38 injection supports the hypothesis that catestatin manipulates the intracellular environment within sympathetic neurons in a way that increases responses to PACAP.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Cromogranina A/farmacología , Fragmentos de Péptidos/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Médula Espinal/efectos de los fármacos , Animales , Sistema Cardiovascular/efectos de los fármacos , Cromogranina A/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Inyecciones Espinales , Masculino , Modelos Animales , Fragmentos de Péptidos/administración & dosificación , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/administración & dosificación , Ratas , Ratas Sprague-Dawley , Médula Espinal/fisiología , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiología , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacologíaRESUMEN
Hypertension is a major cause of morbidity. The neuropeptide catestatin [human chromogranin A-(352-372)] is a peptide product of the vesicular protein chromogranin A. Studies in the periphery and in vitro studies show that catestatin blocks nicotine-stimulated catecholamine release and interacts with ß-adrenoceptors and histamine receptors. Catestatin immunoreactivity is present in the rostral ventrolateral medulla (RVLM), a key site for blood pressure control in the brain stem. Recently, we reported that microinjection of catestatin into the RVLM is sympathoexcitatory and increases barosensitivity. Here, we report the effects of microinjection of catestatin (1 mM, 50 nl) into the caudal ventrolateral medulla (CVLM) in urethane-anesthetized, bilaterally vagotomized, artificially ventilated Sprague-Dawley rats (n = 8). We recorded resting arterial pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and measured cardiovascular homeostatic reflexes. Homeostatic reflexes were evaluated by measuring cardiovascular responses to carotid baroreceptor and peripheral chemoreceptor activation. Catestatin decreased basal levels of arterial pressure (-23 ± 4 mmHg), sympathetic nerve activity (-26.6 ± 5.7%), heart rate (-19 ± 5 bpm), and phrenic nerve amplitude (-16.8 ± 3.3%). Catestatin caused a 15% decrease in phrenic inspiratory period (T(i)) and a 16% increase in phrenic expiratory period (T(e)) but had no net effect on the phrenic interburst interval (T(tot)). Catestatin decreased sympathetic barosensitivity by 63.6% and attenuated the peripheral chemoreflex (sympathetic nerve response to brief hypoxia; range decreased 39.9%; slope decreased 30.1%). The results suggest that catestatin plays an important role in central cardiorespiratory control.
Asunto(s)
Barorreflejo/efectos de los fármacos , Células Quimiorreceptoras/efectos de los fármacos , Cromogranina A/metabolismo , Bulbo Raquídeo/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Simpaticolíticos/farmacología , Animales , Barorreflejo/fisiología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Células Quimiorreceptoras/citología , Células Quimiorreceptoras/fisiología , Cromogranina A/administración & dosificación , Cromogranina A/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Hipoxia/fisiopatología , Masculino , Bulbo Raquídeo/citología , Bulbo Raquídeo/fisiología , Microinyecciones , Modelos Animales , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/metabolismo , Nervio Frénico/efectos de los fármacos , Nervio Frénico/fisiología , Ratas , Ratas Sprague-Dawley , Sistema Nervioso Simpático/fisiología , Simpaticolíticos/administración & dosificaciónRESUMEN
The fundamental role and corollary effects of neuropeptides that govern cardiorespiratory control in the brain stem are poorly understood. One such regulatory peptide, catestatin [Cts, human chromogranin A-(352-372)], noncompetitively inhibits nicotinic-cholinergic-stimulated catecholamine release. Previously, we demonstrated the presence of chromogranin A mRNA in brain stem neurons that are important for the maintenance of arterial pressure. In the present study, using immunofluorescence histochemistry, we show that Cts immunoreactivity is colocalized with tyrosine hydroxylase in C1 neurons of the rostral ventrolateral medulla (RVLM, n = 3). Furthermore, we investigated the effects of Cts on resting blood pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and adaptive reflexes. Cts (1 mM in 50 nl or 100 µM in 50-100 nl) was microinjected into the RVLM in urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats (n = 19). Cardiovascular responses to stimulation of carotid baroreceptors, peripheral chemoreceptors, and the sciatic nerve (somatosympathetic reflex) were analyzed. Cts (1 mM in 50 nl) increased resting arterial pressure (28 ± 3 mmHg at 2 min postinjection), sympathetic nerve activity (15 ± 3% at 2 min postinjection), and phrenic discharge amplitude (31 ± 4% at 10 min postinjection). Cts increased sympathetic barosensitivity 40% (slope increased from -0.05 ± 0.01 before Cts to -0.07 ± 0.01 after Cts) and attenuated the somatosympathetic reflex [1st peak: 36% (from 132 ± 32.1 to 84.0 ± 17.0 µV); 2nd peak: 44% (from 65.1 ± 21.4 to 36.6 ± 14.1 µV)] and chemoreflex (blood pressure response to anoxia decreased 55%, sympathetic response decreased 46%). The results suggest that Cts activates sympathoexcitatory bulbospinal neurons in the RVLM and plays an important regulatory role in adaptive reflexes.
Asunto(s)
Cromogranina A/metabolismo , Cromogranina A/farmacología , Bulbo Raquídeo/efectos de los fármacos , Neuronas/efectos de los fármacos , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/farmacología , Reflejo/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Análisis de Varianza , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Células Quimiorreceptoras/metabolismo , Técnica del Anticuerpo Fluorescente , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Bulbo Raquídeo/fisiología , Neuronas/fisiología , Ratas , Ratas Sprague-Dawley , Reflejo/fisiología , Sistema Nervioso Simpático/fisiología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Catestatin (Cts; human chromogranin A(352-372)) is a neuropeptide derived from chromogranin A (ChgA). In the periphery it is released from the terminals of preganglionic neurons. In the adrenal medulla it inhibits catecholamine release by non-competitively antagonizing nicotinic cholinergic receptors. ChgA is present in the central nervous system, but the extent to which it is present within bulbospinal sympathoexcitatory neurons is unknown. We investigated the distribution of ChgA in the brainstem and its relationship to sympathoexcitatory neurons by combining immunofluorescence and in situ hybridization. A possible role for Cts in modulating the effect of other neurotransmitter systems in the spinal cord was examined by intrathecal injection of Cts, in conjunction with nicotine (1 microg-100 microg) and isoproterenol (0.12 microg-2.5 microg), in the anesthetized rat. Cts attenuated the hypotensive effect of isoproterenol on mean arterial pressure (maximum dose, 2.5 microg isoproterenol; -27 mmHg pre-Cts to -18 mmHg post-Cts), splanchnic sympathetic nerve activity (at 2.5 microg isoproterenol; 10.5% pre-Cts to 2.4% post-Cts), HR (at 2.5 microg isoproterenol; 1.1% pre-Cts to -1.6% post-Cts), and the dp/dt max of carotid pulse pressure (at 2.5 microg isoproterenol 17.3% pre-Cts to 9.3% post-Cts). Cts attenuated the hypertensive effect of nicotine on mean arterial pressure (at 10 microg nicotine, 19.3 mmHg pre-Cts to 6.8 mmHg post-Cts), splanchnic sympathetic nerve activity (at 10 microg nicotine, 10.7% pre-Cts to 4.5% post-Cts), and HR (at 10 microg nicotine, 4.1% pre-Cts to 2.0% post-Cts). The results indicate that Cts antagonizes both central nicotinic acetylcholine receptors and beta-adrenoceptors that are involved in cardiovascular regulation in vivo.