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1.
Vis Neurosci ; 39: E007, 2022 11 02.
Article in English | MEDLINE | ID: mdl-36321413

ABSTRACT

Studies in the greater galago have not provided a comprehensive description of the organization of eye-specific retino-geniculate-cortical projections to the recipient layers in V1. Here we demonstrate the overall patterns of ocular dominance domains in layers III, IV, and VI revealed following a monocular injection of the transneuronal tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP). We also correlate these patterns with the array of cytochrome oxidase (CO) blobs in tangential sections through the unfolded and flattened cortex. In layer IV, we observed for the first time that eye-specific domains form an interconnected pattern of bands 200-250 µm wide arranged such that they do not show orientation bias and do not meet the V1 border at right angles, as is the case in macaques. We also observed distinct WGA-HRP labeled patches in layers III and VI. The patches in layer III, likely corresponding to patches of K lateral geniculate nucleus (LGN) input, align with layer IV ocular dominance columns (ODCs) of the same eye dominance and overlap partially with virtually all CO blobs in both hemispheres, implying that CO blobs receive K LGN input from both eyes. We further found that CO blobs straddle the border between layer IV ODCs, such that the distribution of CO staining is approximately equal over ipsilateral and contralateral ODCs. These results, together with studies showing that a high percentage of cells in CO blobs are monocular, suggest that CO blobs consist of ipsilateral and contralateral subregions that are in register with underlying layer IV ODCs of the same eye dominance. In macaques and humans, CO blobs are centered on ODCs in layer IV. Our finding that CO blobs in galago straddle the border of neighboring layer IV ODCs suggests that this novel feature may represent an alternative way by which visual information is processed by eye-specific modular architecture in mammalian V1.


Subject(s)
Galagidae , Visual Cortex , Animals , Humans , Electron Transport Complex IV , Visual Cortex/physiology , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate , Primary Visual Cortex , Geniculate Bodies/physiology , Galago , Macaca , Mammals
2.
Behav Brain Res ; 359: 853-860, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30041008

ABSTRACT

Typical responses in muscle following acute aerobic exercise have been well documented, but the responses in brain have remained relatively unexplored. Recent reports suggest that a single bout of aerobic exercise can prime motor regions of the human brain to experience use-dependent plasticity, however, the mechanisms underlying this priming phenomenon are unclear. As a result, we asked whether a graded test to exhaustion (GXT), the most widely employed test to examine relationships between exercise and integrated responses within the musculoskeletal, cardiopulmonary, and neuropsychological systems, would be able to upregulate the expression of plasticity-related proteins in sensorimotor cortex in rats. We examined immediate responses in animals following either a GXT, or two resting conditions: non-exercising treadmill controls (TC), and acclimatization controls (AC). Young, male Sprague-Dawley rats (n = 20) on a reverse light cycle (12 h/12 h) were exposed to a treadmill acclimatization procedure consisting of 8 days of increasing exercise intensity (10 m/min up to 25 m/min) for 10 min at the same time each day. The acclimatization was followed by 2 days of rest to reduce any carryover effects. On testing day, rats performed either a GXT, or rested (TC and AC), were then sacrificed and sensorimotor cortex dissected. Homogenates were probed for a physiological marker of stress (HSP 70), and plasticity-related proteins (CaMKII, GluN2A, GluN1, GluA1, GluA2) by Western blotting analysis. Both our acclimatization protocol and single event GXT yielded no observable differences in protein expression, suggesting that single session exercise does not prime brain via altered plasticity-related protein expression.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Oxygen Consumption/physiology , Physical Conditioning, Animal , Receptors, N-Methyl-D-Aspartate/metabolism , Sensorimotor Cortex/physiology , Analysis of Variance , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Dextrans/metabolism , Exercise Test , Male , Rats , Rats, Sprague-Dawley , Time Factors , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
3.
Brain Struct Funct ; 223(1): 371-390, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28852862

ABSTRACT

The zona incerta contains GABAergic neurons that project to the superior colliculus in the cat and rat, suggesting that it plays a role in gaze changes. However, whether this incertal connection represents a general mammalian pattern remains to be determined. We used neuronal tracers to examine the zona incerta connections with the midbrain tectum in the gray squirrel and macaque monkey. Collicular injections in both species revealed that most incertotectal neurons lay in the ventral layer, but anterogradely labeled tectoincertal terminals were found in both the dorsal and ventral layers. In the monkey, injections of the pretectum also produced retrograde labeling, but mainly in the dorsal layer. The dendritic fields of incertotectal and incertopretectal cells were generally contained within the layer inhabited by their somata. The macaque, but not the squirrel, zona incerta extended dorsolaterally, within the external medullary lamina. Zona incerta injections produced retrogradely labeled neurons in the superior colliculus of both species. In the squirrel, most cells inhabited the lower sublamina of the intermediate gray layer, but in the monkey, they were scattered throughout the deeper layers. Labeled cells were present among the pretectal nuclei in both species. Labeled terminals were concentrated in the lower sublamina of the intermediate gray layer of both species, but were dispersed among the pretectal nuclei. In summary, an incertal projection that is concentrated on the collicular motor output layers and that originates in the ventral layer of the ipsilateral zona incerta is a common mammalian feature, suggesting an important role in collicular function.


Subject(s)
Brain Mapping , Neural Pathways/physiology , Superior Colliculi/anatomy & histology , Zona Incerta/anatomy & histology , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Dextrans/metabolism , Macaca/anatomy & histology , Sciuridae/anatomy & histology , Species Specificity , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
4.
Brain Struct Funct ; 223(4): 1713-1729, 2018 May.
Article in English | MEDLINE | ID: mdl-29196811

ABSTRACT

Mirror neurons (MNs) are a class of cells originally discovered in the monkey ventral premotor cortex (PMv) and inferior parietal lobule (IPL). They discharge during both action execution and action observation and appear to play a crucial role in understanding others' actions. It has been proposed that the mirror mechanism is based on a match between the visual description of actions, encoded in temporal cortical regions, and their motor representation, provided by PMv and IPL. However, neurons responding to action observation have been recently found in other cortical regions, suggesting that the mirror mechanism relies on a wider network. Here we provide the first description of this network by injecting neural tracers into physiologically identified IPL and PMv sectors containing hand MNs. Our results show that these sectors are reciprocally connected, in line with the current view, but IPL MN sectors showed virtually no direct connection with temporal visual areas. In addition, we found that PMv and IPL MN sectors share connections with several cortical regions, including the dorsal and mesial premotor cortex, the primary motor cortex, the secondary somatosensory cortex, the mid-dorsal insula and the ventrolateral prefrontal cortex, as well as subcortical structures, such as motor and polysensory thalamic nuclei and the mid-dorsal claustrum. We propose that each of these regions constitutes a node of an "extended network", through which information relative to ongoing movements, social context, environmental contingencies, abstract rules, and internal states can influence MN activity and contribute to several socio-cognitive functions.


Subject(s)
Brain Mapping , Hand/physiology , Mirror Neurons/physiology , Motor Cortex/cytology , Parietal Lobe/cytology , Psychomotor Performance/physiology , Action Potentials/physiology , Afferent Pathways , Animals , Cholera Toxin/metabolism , Female , Macaca nemestrina , Male , Motor Cortex/physiology , Parietal Lobe/physiology , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
5.
Neuroscience ; 365: 158-178, 2017 Dec 04.
Article in English | MEDLINE | ID: mdl-28993238

ABSTRACT

Little is known about how proprioceptive signals arising from muscles reach to higher brain regions such as the cerebral cortex. We have recently shown that a particular thalamic region, the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM), receives the proprioceptive signals from jaw-closing muscle spindles (JCMSs) in rats. In this study, we further addressed how the orofacial thalamic inputs from the JCMSs were transmitted from the thalamus (VPMcvm) to the cerebral cortex in rats. Injections of a retrograde and anterograde neuronal tracer, wheat-germ agglutinin-conjugated horseradish peroxidase (WGA-HRP), into the VPMcvm demonstrated that the thalamic pathway terminated mainly in a rostrocaudally narrow area in the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of the secondary somatosensory cortex (dGIrvs2). We also electrophysiologically confirmed that the dGIrvs2 received the proprioceptive inputs from JCMSs. To support the anatomical evidence of the VPMcvm-dGIrvs2 pathway, injections of a retrograde neuronal tracer Fluorogold into the dGIrvs2 demonstrated that the thalamic neurons projecting to the dGIrvs2 were confined in the VPMcvm and the parvicellular part of ventral posterior nucleus. In contrast, WGA-HRP injections into the lingual nerve area of core VPM demonstrated that axon terminals were mainly labeled in the core regions of the primary and secondary somatosensory cortices, which were far from the dGIrvs2. These results suggest that the dGIrvs2 is a specialized cortical region receiving the orofacial proprioceptive inputs. Functional contribution of the revealed JCMSs-VPMcvm-dGIrvs2 pathway to Tourette syndrome is also discussed.


Subject(s)
Cerebral Cortex/physiology , Facial Muscles/innervation , Neural Pathways/physiology , Proprioception/physiology , Thalamus/physiology , Animals , Brain Mapping , Electric Stimulation , Evoked Potentials/physiology , Facial Muscles/physiology , Functional Laterality , Jaw/physiology , Male , Rats , Rats, Wistar , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
6.
J Neurosci ; 36(12): 3441-52, 2016 Mar 23.
Article in English | MEDLINE | ID: mdl-27013674

ABSTRACT

Respiratory complications in patients with spinal cord injury (SCI) are common and have a negative impact on the quality of patients' lives. Systemic administration of drugs that improve respiratory function often cause deleterious side effects. The present study examines the applicability of a novel nanotechnology-based drug delivery system, which induces recovery of diaphragm function after SCI in the adult rat model. We developed a protein-coupled nanoconjugate to selectively deliver by transsynaptic transport small therapeutic amounts of an A1 adenosine receptor antagonist to the respiratory centers. A single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the systemic therapeutic drug dose. The reduction of the systemic dose may obviate the side effects. The recovery lasted for 4 weeks (the longest period studied). These findings have translational implications for patients with respiratory dysfunction after SCI. SIGNIFICANCE STATEMENT: The leading causes of death in humans following SCI are respiratory complications secondary to paralysis of respiratory muscles. Systemic administration of methylxantines improves respiratory function but also leads to the development of deleterious side effects due to actions of the drug on nonrespiratory sites. The importance of the present study lies in the novel drug delivery approach that uses nanotechnology to selectively deliver recovery-inducing drugs to the respiratory centers exclusively. This strategy allows for a reduction in the therapeutic drug dose, which may reduce harmful side effects and markedly improve the quality of life for SCI patients.


Subject(s)
Diaphragm/physiopathology , Receptor, Adenosine A1/metabolism , Respiratory Paralysis/drug therapy , Respiratory Paralysis/physiopathology , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/physiopathology , Xanthines/administration & dosage , Adenosine A1 Receptor Antagonists/administration & dosage , Adenosine A1 Receptor Antagonists/chemistry , Animals , Diaphragm/drug effects , Male , Muscle Strength/drug effects , Nanoconjugates/administration & dosage , Nanoconjugates/chemistry , Rats , Rats, Sprague-Dawley , Recovery of Function/drug effects , Respiratory Mechanics/drug effects , Respiratory Paralysis/etiology , Spinal Cord Injuries/complications , Treatment Outcome , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/chemistry , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/pharmacokinetics , Xanthines/chemistry
7.
Brain Res ; 1636: 21-42, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-26835561

ABSTRACT

The effects of 17ß-estradiol (E) on the distribution and density of brainstem projections of small or large diameter primary vagal afferents were investigated in Wistar rats using transganglionic transport of wheat germ agglutinin- (WGA; preferentially transported by non-myelinated afferent C-fibers; 2%), or cholera toxin B-subunit- (CTB, 5%; preferentially transported by large myelinated afferent A-fibers) conjugated horseradish peroxidase (HRP) in combination with the tetramethylbenzidine method in age matched ovariectomized (OVX) only or OVX and treated with E (OVX+E; 30 pg/ml plasma) females for 12 weeks. Additionally, these projections were compared to aged matched males. Unilateral microinjection of WGA-HRP into the nodose ganglion resulted in dense anterograde labeling bilaterally, with an ipsilateral predominance in several subnuclei of the nucleus of the solitary tract (NTS) and in area postrema that was greatest in OVX+E animals compared to OVX only and males. Moderately dense anterograde labeling was also observed in paratrigeminal nucleus (PAT) of the OVX+E animals. CTB-HRP produced less dense anterograde labeling in the NTS complex, but had a wider distribution within the brainstem including the area postrema, dorsal motor nucleus of the vagus, PAT, the nucleus ambiguus complex and ventrolateral medulla in all groups. The distribution of CTB-HRP anterograde labeling was densest in OVX+E, less dense in OVX only females and least dense in male rats. Little, if any, labeling was found within PAT in males using either WGA-or CTB-HRP. Taken together, these data suggest that small, non-myelinated (WGA-labeled) and large myelinated (CTB-labeled) diameter vagal afferents projecting to brainstem autonomic areas are differentially affected by circulating levels of estrogen. These effects of estrogen on connectivity may contribute to the sex differences observed in central autonomic mechanisms between gender, and in females with and without estrogen.


Subject(s)
Brain Stem/anatomy & histology , Estradiol/pharmacology , Estrogens/pharmacology , Neurons, Afferent/drug effects , Sex Characteristics , Vagus Nerve/physiology , Animals , Brain Stem/metabolism , Cholera Toxin/metabolism , Female , Functional Laterality , Horseradish Peroxidase/metabolism , Male , Neurons, Afferent/physiology , Nodose Ganglion/physiology , Ovariectomy , Rats , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
8.
J Comp Neurol ; 524(7): 1494-526, 2016 May 01.
Article in English | MEDLINE | ID: mdl-26519356

ABSTRACT

A complete unilateral lesion of the dorsal column somatosensory pathway in the upper cervical spinal cord deactivates neurons in the hand region in contralateral somatosensory cortex (areas 3b and 1). Over weeks to months of recovery, parts of the hand region become reactivated by touch on the hand or face. To determine whether changes in cortical connections potentially contribute to this reactivation, we injected tracers into electrophysiologically identified locations in cortex of area 3b representing the reactivated hand and normally activated face in adult squirrel monkeys. Our results indicated that even when only partially reactivated, most of the expected connections of area 3b remained intact. These intact connections include the majority of intrinsic connections within area 3b; feedback connections from area 1, secondary somatosensory cortex (S2), parietal ventral area (PV), and other cortical areas; and thalamic inputs from the ventroposterior lateral nucleus (VPL). In addition, tracer injections in the reactivated hand region of area 3b labeled more neurons in the face and shoulder regions of area 3b than in normal monkeys, and injections in the face region of area 3b labeled more neurons in the hand region. Unexpectedly, the intrinsic connections within area 3b hand cortex were more widespread after incomplete dorsal column lesions (DCLs) than after a complete DCL. Although these additional connections were limited, these changes in connections may contribute to the reactivation process after injuries. J. Comp. Neurol. 524:1494-1526, 2016. © 2015 Wiley Periodicals, Inc.


Subject(s)
Functional Laterality/physiology , Hand/innervation , Neural Pathways/physiology , Neurons/physiology , Somatosensory Cortex/cytology , Somatosensory Cortex/physiology , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Brain Mapping , Cholera Toxin/metabolism , Dextrans/metabolism , Hand Strength/physiology , Range of Motion, Articular/physiology , Saimiri , Vesicular Glutamate Transport Protein 2/metabolism , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
9.
J Comp Neurol ; 523(17): 2570-98, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-25975699

ABSTRACT

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown.


Subject(s)
Macaca fascicularis/anatomy & histology , Prefrontal Cortex/anatomy & histology , Temporal Lobe/anatomy & histology , Afferent Pathways/physiology , Amidines/metabolism , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Brain Mapping , Dextrans/metabolism , Fasting , Male , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
10.
J Comp Neurol ; 523(12): 1809-23, 2015 Aug 15.
Article in English | MEDLINE | ID: mdl-25684641

ABSTRACT

Mammalian extraocular muscles contain singly innervated twitch muscle fibers (SIF) and multiply innervated nontwitch muscle fibers (MIF). In monkey, MIF motoneurons lie around the periphery of oculomotor nuclei and have premotor inputs different from those of the motoneurons inside the nuclei. The most prominent MIF motoneuron group is the C group, which innervates the medial rectus (MR) and inferior rectus (IR) muscle. To explore the organization of both cell groups within the C group, we performed small injections of choleratoxin subunit B into the myotendinous junction of MR or IR in monkeys. In three animals the IR and MR myotendinous junction of one eye was injected simultaneously with different tracers (choleratoxin subunit B and wheat germ agglutinin). This revealed that both muscles were supplied by two different, nonoverlapping populations in the C group. The IR neurons lie adjacent to the dorsomedial border of the oculomotor nucleus, whereas MR neurons are located farther medially. A striking feature was the differing pattern of dendrite distribution of both cell groups. Whereas the dendrites of IR neurons spread into the supraoculomotor area bilaterally, those of the MR neurons were restricted to the ipsilateral side and sent a focused bundle dorsally to the preganglionic neurons of the Edinger-Westphal nucleus, which are involved in the "near response." In conclusion, MR and IR are innervated by independent neuron populations from the C group. Their dendritic branching pattern within the supraoculomotor area indicates a participation in the near response providing vergence but also reflects their differing functional roles.


Subject(s)
Macaca mulatta/anatomy & histology , Motor Neurons/cytology , Oculomotor Muscles/innervation , Oculomotor Nuclear Complex/cytology , Animals , Cholera Toxin , Dendrites , Immunohistochemistry , Neuroanatomical Tract-Tracing Techniques , Neuronal Tract-Tracers , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
11.
Hippocampus ; 25(9): 977-92, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25616174

ABSTRACT

The hippocampal formation and anterior thalamic nuclei form part of an interconnected network thought to support memory. A central pathway in this mnemonic network comprises the direct projections from the hippocampal formation to the anterior thalamic nuclei, projections that, in the primate brain, originate in the subicular cortices to reach the anterior thalamic nuclei by way of the fornix. In the rat brain, additional pathways involving the internal capsule have been described, linking the dorsal subiculum to the anteromedial thalamic nucleus, as well as the postsubiculum to the anterodorsal thalamic nucleus. Confirming such pathways is essential in order to appreciate how information is transferred from the hippocampal formation to the anterior thalamus and how it may be disrupted by fornix pathology. Accordingly, in the present study, pathway tracers were injected into the anterior thalamic nuclei and the dorsal subiculum of rats with fornix lesions. Contrary to previous descriptions, projections from the subiculum to the anteromedial thalamic nucleus overwhelmingly relied on the fornix. Dorsal subiculum projections to the majority of the anteroventral nucleus also predominantly relied on the fornix, although postsubicular inputs to the lateral dorsal part of the anteroventral nucleus, as well as to the anterodorsal and laterodorsal thalamic nuclei, largely involved a nonfornical pathway, via the internal capsule.


Subject(s)
Anterior Thalamic Nuclei/cytology , Hippocampus/cytology , Neural Pathways/physiology , Amidines/metabolism , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Dextrans/metabolism , Fornix, Brain/injuries , Fornix, Brain/physiology , Functional Laterality , Male , Rats , Rats, Wistar , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
12.
J Craniofac Surg ; 25(5): 1882-4, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25119405

ABSTRACT

Clearing the somatotopic organization of trigeminal ganglion can help us to improve the precision of treatment for trigeminal neuralgia. The distribution of primary afferent perikarya of 3 branches of trigeminal nerve in the trigeminal ganglion was investigated in the rabbit, and 3D model was reconstructed then. After application of wheat germ agglutinin-horseradish peroxidase and DiI to the cut endings of the 3 branches of trigeminal nerve, ophthalmic cells were found in the anteromedial part of the trigeminal ganglion, mandibular cells in the posterolateral part, and maxillary cells in the middle part. The results suggest that the somatotopic organization of the ganglion in rabbits is a mediolateral direction reflecting the mediolateral order of the ophthalmic, maxillary, and mandibular nerves.


Subject(s)
Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Trigeminal Ganglion/anatomy & histology , Trigeminal Nerve/anatomy & histology , Animals , Carbocyanines , Female , Fluorescent Dyes , Male , Mandibular Nerve/anatomy & histology , Maxillary Nerve/anatomy & histology , Molecular Probes , Nerve Fibers/ultrastructure , Neural Pathways/anatomy & histology , Neurons, Afferent/cytology , Ophthalmic Nerve/anatomy & histology , Rabbits , Sensory Receptor Cells/cytology , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
13.
J Neurosci ; 34(31): 10379-93, 2014 Jul 30.
Article in English | MEDLINE | ID: mdl-25080597

ABSTRACT

Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation.


Subject(s)
Brain-Derived Neurotrophic Factor/deficiency , Intestines/physiology , Microfilament Proteins/genetics , Muscle Proteins/genetics , Neurons, Afferent/physiology , Satiation/physiology , Vagus Nerve/physiology , Analysis of Variance , Animals , Axons/physiology , Body Composition/genetics , Body Weight/genetics , Brain-Derived Neurotrophic Factor/genetics , Eating/genetics , Feeding Behavior/physiology , Intestines/innervation , Mice , Mice, Transgenic , Nodose Ganglion/cytology , Nodose Ganglion/metabolism , RNA, Messenger/metabolism , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
14.
J Comp Neurol ; 522(18): 3978-4002, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-24706263

ABSTRACT

Preganglionic motoneurons supplying the ciliary ganglion control lens accommodation and pupil diameter. In cats, these motoneurons make up the preganglionic Edinger-Westphal population, which lies rostral, dorsal, and ventral to the oculomotor nucleus. A recent cat study suggested that caudal motoneurons control the lens and rostral motoneurons control the pupil. This led us to examine the morphology, ultrastructure, and pretectal inputs of these populations. Preganglionic motoneurons retrogradely labeled by introducing tracer into the cat ciliary ganglion generally fell into two morphologic categories. Fusiform neurons were located rostrally, in the anteromedian nucleus and between the oculomotor nuclei. Multipolar neurons were found caudally, dorsal and ventral to the oculomotor nucleus. The dendrites of preganglionic motoneurons within the anteromedian nucleus crossed the midline, providing a possible basis for consensual responses. Ultrastructurally, several different classes of synaptic profiles contact preganglionic motoneurons, suggesting that their activity may be modified by a variety of inputs. Furthermore, there were differences in the synaptic populations contacting the rostral vs. caudal populations, supporting the contention that these populations display functional differences. Anterogradely labeled pretectal terminals were observed in close association with labeled preganglionic motoneurons, particularly in the rostral population. Ultrastructural analysis revealed that these terminals, packed with clear, spherical vesicles, made asymmetric synaptic contacts onto motoneurons in the rostral population, indicating that these cells serve the pupillary light reflex. Thus, the preganglionic motoneurons found in the cat display morphologic, ultrastructural, and connectional differences suggesting that this rostral preganglionic population is specialized for pupil control, whereas more caudal elements control the lens.


Subject(s)
Motor Neurons/cytology , Reflex, Pupillary , Animals , Cats , Edinger-Westphal Nucleus/cytology , Edinger-Westphal Nucleus/physiology , Female , Ganglia, Parasympathetic/cytology , Ganglia, Parasympathetic/physiology , Male , Microscopy, Electron , Motor Neurons/physiology , Olivary Nucleus/cytology , Olivary Nucleus/physiology , Photomicrography , Pretectal Region/cytology , Pretectal Region/physiology , Reflex, Pupillary/physiology , Retina/cytology , Retina/physiology , Synapses/physiology , Synapses/ultrastructure , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
15.
J Comp Neurol ; 522(18): 3960-77, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-24706328

ABSTRACT

The central pathways subserving the feline pupillary light reflex were examined by defining retinal input to the olivary pretectal nucleus (OPt), the midbrain projections of this nucleus, and the premotor neurons within it. Unilateral intravitreal wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injections revealed differences in the pattern of retinal OPt termination on the two sides. Injections of WGA-HRP into OPt labeled terminals bilaterally in the anteromedian nucleus, and to a lesser extent in the supraoculomotor area, centrally projecting Edinger-Westphal nucleus, and nucleus of the posterior commissure. Labeled terminals, as well as retrogradely labeled multipolar cells, were present in the contralateral OPt, indicating a commissural pathway. Injections of WGA-HRP into the anteromedian nucleus labeled fusiform premotor neurons within the OPt, as well as multipolar cells in the nucleus of the posterior commissure. Connections between retinal terminals and the pretectal premotor neurons were characterized by combining vitreous chamber and anteromedian nucleus injections of WGA-HRP in the same animal. Fusiform-shaped, retrogradely labeled cells fell within the anterogradely labeled retinal terminal field in the OPt. Ultrastructural analysis revealed labeled retinal terminals containing clear spherical vesicles. They contacted labeled pretectal premotor neurons via asymmetric synaptic densities. These results provide an anatomical substrate for the pupillary light reflex in the cat. Pretectal premotor neurons receive direct retinal input via synapses suggestive of an excitatory drive, and project directly to nuclei containing preganglionic motoneurons. These projections are concentrated in the anteromedian nucleus, indicating its involvement in the pupillary light reflex.


Subject(s)
Olivary Nucleus/anatomy & histology , Pretectal Region/anatomy & histology , Reflex, Pupillary , Animals , Cats , Edinger-Westphal Nucleus/anatomy & histology , Edinger-Westphal Nucleus/physiology , Female , Male , Microscopy, Electron , Motor Cortex/anatomy & histology , Motor Cortex/physiology , Neurons/cytology , Neurons/physiology , Olivary Nucleus/physiology , Photomicrography , Pretectal Region/physiology , Reflex, Pupillary/physiology , Retina/anatomy & histology , Retina/physiology , Synapses/physiology , Synapses/ultrastructure , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
16.
Somatosens Mot Res ; 31(3): 141-51, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24738912

ABSTRACT

Trigeminal (V) nucleus principalis (PrV) is the requisite brainstem nucleus in the whisker-to-barrel cortex model system that is widely used to reveal mechanisms of map formation and information processing. Yet, little is known of the actual PrV circuitry. In the ventral "barrelette" portion of the adult mouse PrV, relationships between V primary afferent terminals, thalamic-projecting PrV neurons, and gamma-aminobutyric acid (GABA)-ergic terminals were analyzed in the electron microscope. Primary afferents, thalamic-projecting cells, and GABAergic terminals were labeled, respectively, by Neurobiotin injections in the V ganglion, horseradish peroxidase injections in the thalamus, and postembedding immunogold histochemistry. Primary afferent terminals (Neurobiotin- and glutamate-immunoreactive) display asymmetric and multiple synapses predominantly upon the distal dendrites and spines of PrV cells that project to the thalamus. Primary afferents also synapse upon GABAergic terminals. GABAergic terminals display symmetric synapses onto primary afferent terminals, the somata and dendrites (distal, mostly) of thalamic-projecting neurons, and GABAergic dendrites. Thus, primary afferent inputs through the PrV are subject to pre- and postsynaptic GABAergic influences. As such, circuitry exists in PrV "barrelettes" for primary afferents to directly activate thalamic-projecting and inhibitory local circuit cells. The latter are synaptically associated with themselves, the primary afferents, and with the thalamic-projecting neurons. Thus, whisker-related primary afferent inputs through PrV projection neurons are pre- and postsynaptically modulated by local circuits.


Subject(s)
Afferent Pathways/physiology , Afferent Pathways/ultrastructure , Nerve Net/diagnostic imaging , Trigeminal Nuclei/ultrastructure , Vibrissae/innervation , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Female , Glutamic Acid/metabolism , Male , Mice , Microscopy, Immunoelectron , Synapses/metabolism , Synapses/ultrastructure , Ultrasonography , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism , gamma-Aminobutyric Acid/metabolism
17.
Cereb Cortex ; 24(4): 1054-65, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23236207

ABSTRACT

We found that the macaque inferior parietal (PFG and anterior intraparietal [AIP]), ventral premotor (F5p and F5a), and ventrolateral prefrontal (rostral 46vc and intermediate 12r) areas forming a network involved in controlling purposeful hand actions ("lateral grasping network") are a source of corticotectal projections. Based on injections of anterograde tracers at the cortical level, the results showed that all these areas displayed relatively dense projections to the intermediate and deep gray layers of the ipsilateral superior colliculus (SC) and to the ventrally adjacent mesencephalic reticular formation. In the SC, the labeling tended to be richer in the lateral part along almost the entire rostro-caudal extent, that is, in regions controlling microsaccades and downward gaze shifts and hosting arm-related neurons and neurons modulated by the contact of the hand with the target. These projections could represent a descending motor pathway for controlling proximo-distal arm synergies. Furthermore, they could broadcast to the SC information related to hand action goals and object affordances extraction and selection. This information could be used in the SC for controlling orienting behavior (gaze and reaching movements) to the targets of object-oriented actions and for the eye-hand coordination necessary for appropriate hand-object interactions.


Subject(s)
Brain Mapping , Cerebral Cortex/physiology , Goals , Hand/physiology , Parietal Lobe/physiology , Superior Colliculi/physiology , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Dextrans/metabolism , Isoquinolines/metabolism , Macaca , Neural Pathways/physiology , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
18.
J Comp Neurol ; 522(3): 546-72, 2014 Feb 15.
Article in English | MEDLINE | ID: mdl-23853118

ABSTRACT

We placed injections of anatomical tracers into representations of the tongue, teeth, and face in the primary somatosensory cortex (area 3b) of macaque monkeys. Our injections revealed strong projections to representations of the tongue and teeth from other parts of the oral cavity responsive region in 3b. The 3b face also provided input to the representations of the intraoral structures. The primary representation of the face showed a pattern of intrinsic connections similar to that of the mouth. The area 3b hand representation provided little to no input to either the mouth or the face representations. The mouth and face representations of area 3b received projections from the presumptive oral cavity and face regions of other somatosensory areas in the anterior parietal cortex and the lateral sulcus, including areas 3a, 1, 2, the second somatosensory area (S2), the parietal ventral area (PV), and cortex that may include the parietal rostral (PR) and ventral somatosensory (VS) areas. Additional inputs came from primary motor (M1) and ventral premotor (PMv) areas. This areal pattern of projections is similar to the well-studied pattern revealed by tracer injections in regions of 3b representing the hand. The tongue representation appeared to be unique in area 3b in that it also received inputs from areas in the anterior upper bank of the lateral sulcus and anterior insula that may include the primary gustatory area (area G) and other cortical taste-processing areas, as well as a region of lateral prefrontal cortex (LPFC) lining the principal sulcus.


Subject(s)
Face/innervation , Nerve Net/physiology , Somatosensory Cortex/cytology , Somatosensory Cortex/physiology , Tongue/innervation , Tooth/innervation , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Brain Mapping , Dextrans/metabolism , Functional Laterality , Macaca mulatta , Macaca radiata , Physical Stimulation , Rats , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
19.
J Comp Neurol ; 522(3): 626-41, 2014 Feb 15.
Article in English | MEDLINE | ID: mdl-23897455

ABSTRACT

There are two muscle fiber types in extraocular muscles: those receiving a single motor endplate, termed singly innervated fibers (SIFs), and those receiving multiple small terminals along their length, termed multiply innervated fibers (MIFs). In monkeys, these two fiber types receive input from different motoneuron pools: SIF motoneurons found within the extraocular motor nuclei, and MIF motoneurons found along their periphery. For the monkey medial rectus muscle, MIF motoneurons are found in the C-group, while SIF motoneurons lie in the A- and B-groups. We analyzed the somatodendritic morphology and ultrastructure of these three subgroups of macaque medial rectus motoneurons to better understand the structural determinants controlling the two muscle fiber types. The dendrites of A- and B-group motoneurons lay within the oculomotor nucleus, but those of the C-group motoneurons were located outside the nucleus, and extended into the preganglionic Edinger-Westphal nucleus. A- and B-group motoneurons were very similar ultrastructurally. In contrast, C-group motoneurons displayed significantly fewer synaptic contacts on their somata and proximal dendrites, and those contacts were smaller in size and lacked dense-cored vesicles. However, the synaptic structure of C-group distal dendrites was quite similar to that observed for A- and B-group motoneurons. Our anatomical findings suggest that C-group MIF motoneurons have different physiological properties than A- and B-group SIF motoneurons, paralleling their different muscle fiber targets. Moreover, primate C-group motoneurons have evolved a special relationship with the preganglionic Edinger-Westphal nucleus, suggesting these motoneurons play an important role in near triad convergence to support increased near work requirements.


Subject(s)
Motor Neurons/classification , Motor Neurons/physiology , Oculomotor Muscles/innervation , Animals , Electron Microscope Tomography , Macaca fascicularis , Male , Motor Neurons/ultrastructure , Oculomotor Muscles/cytology , Presynaptic Terminals/ultrastructure , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism
20.
J Comp Neurol ; 521(14): 3133-53, 2013 Oct 01.
Article in English | MEDLINE | ID: mdl-23787784

ABSTRACT

A solitary cluster of parvalbumin-positive neurons--the PV1 nucleus--has been observed in the lateral hypothalamus of rodents. In the present study, we mapped the efferent connections of the PV1 nucleus using nonspecific antero- and retrograde tracers in rats, and chemoselective, Cre-dependent viral constructs in parvalbumin-Cre mice. In both species, the PV1 nucleus was found to project mainly to the periaqueductal grey matter (PAG), predominantly ipsilaterally. Indirectly in rats and directly in mice, a discrete, longitudinally oriented cylindrical column of terminal fields (PV1-CTF) was identified ventrolateral to the aqueduct on the edge of the PAG. The PV1-CTF is particularly dense in the rostral portion, which is located in the supraoculomotor nucleus (Su3). It is spatially interrupted over a short stretch at the level of the trochlear nucleus and abuts caudally on a second parvalbumin-positive (PV2) nucleus. The rostral and the caudal portions of the PV1-CTF consist of axonal endings, which stem from neurons scattered throughout the PV1 nucleus. Topographically, the longitudinal orientation of the PV1-CTF accords with that of the likewise longitudinally oriented functional modules of the PAG, but overlaps none of them. Minor terminal fields were identified in a crescentic column of the lateral PAG, as well as in the Edinger-Westphal, the lateral habenular, and the laterodorsal tegmental nuclei. So far, no obvious functions have been attributed to this small, circumscribed column ventrolateral to the aqueduct, the prime target of the PV1 nucleus.


Subject(s)
Hypothalamus/cytology , Neural Pathways/physiology , Neurons/metabolism , Parvalbumins/metabolism , Adenoviridae , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Brain Mapping , Channelrhodopsins , Dextrans/metabolism , Female , Functional Laterality , Green Fluorescent Proteins/genetics , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Male , Mice , Mice, Transgenic , Parvalbumins/genetics , Periaqueductal Gray/cytology , Periaqueductal Gray/metabolism , Rats , Rats, Wistar , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism , Red Fluorescent Protein
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