scholarly journals Local brainstem circuits contribute to reticulospinal output in the mouse

2021 ◽  
Author(s):  
Jeremy W. Chopek ◽  
Ying Zhang ◽  
Robert M Brownstone

ABSTRACTGlutamatergic reticulospinal neurons in the gigantocellular reticular nucleus (GRN) of the medullary reticular formation can function as command neurons, transmitting motor commands to spinal cord circuits. Recent advances in our understanding of this neuron-dense region have been facilitated by the discovery of expression of the transcriptional regulator, Chx10, in excitatory reticulospinal neurons. Here, we address the capacity of local circuitry in the GRN to contribute to reticulospinal output. We define two sub-populations of Chx10-expressing neurons in this region, based on distinct electrophysiological properties and somata size (small and large), and show that these correspond to local interneurons and reticulospinal neurons, respectively. Using focal release of caged-glutamate combined with patch clamp recordings, we demonstrated that Chx10 neurons form microcircuits in which the Chx10 interneurons project to and facilitate the firing of Chx10 reticulospinal neurons. We discuss the implications of these microcircuits in terms of movement selection.SIGNIFICANCE STATEMENTReticulospinal neurons in the medullary reticular formation play a key role in movement. The transcriptional regulator Chx10 defines a population of glutamatergic neurons in this region, a proportion of which have been shown to be involved in stopping, steering, and modulating locomotion. While it has been shown that these neurons integrate descending inputs, we asked whether local processing also ultimately contributes to reticulospinal outputs. Here, we define Chx10-expressing medullary reticular formation interneurons and reticulospinal neurons, and demonstrate how the former modulate the output of the latter. The results shed light on the internal organization and microcircuit formation of reticular formation neurons.

Author(s):  
Jeremy W. Chopek ◽  
Ying Zhang ◽  
Robert M. Brownstone

Glutamatergic reticulospinal neurons in the gigantocellular reticular nucleus (GRN) of the medullary reticular formation can function as command neurons, transmitting motor commands to spinal cord circuits to instruct movement. Recent advances in our understanding of this neuron-dense region have been facilitated by the discovery of expression of the transcriptional regulator, Chx10, in excitatory reticulospinal neurons. Here, we address the capacity of local circuitry in the GRN to contribute to reticulospinal output. We define two sub-populations of Chx10-expressing neurons in this region, based on distinct electrophysiological properties and somata size (small and large), and show that these populations correspond to local interneurons and reticulospinal neurons, respectively. Using focal release of caged glutamate combined with patch clamp recordings, we demonstrated that Chx10 neurons form microcircuits in which the Chx10 local interneurons project to and facilitate the firing of Chx10 reticulospinal neurons. We discuss the implications of these microcircuits in terms of movement selection.


1978 ◽  
Vol 41 (3) ◽  
pp. 821-834 ◽  
Author(s):  
P. W. Wyzinski ◽  
R. W. McCarley ◽  
J. A. Hobson

1. Reticulospinal neurons were identified by antidromic invasion from spinal cord electrodes chronically implanted at C4 in cats. 2. Most of the neuronal population studied lay within the medial portion of the giant cell field from the anterior pontine and to the anterior medullary reticular formation (FTG). A few cells were found in the tegmental reticular nucleus (TRC) which has not previously been known to project to the spinal cord. 3. Extracellular action potentials from the neuronal somata of the identified neurons were recorded continuously throughout naturally occurring sleep-waking cycles. 4. The identified reticulospinal neurons shared three properties, suggesting a generator function in desynchronized sleep (D) (with previously recorded but unidentified FTG neurons): selectivity (or concentration of discharge in D); tonic latency (or firing rate increases beginning several minutes prior to D); and phasic latency (or firing rate increases occurring prior to eye movements within D). 5. The location, discharge properties, and spinal projections of FTG neurons are, thus, all consistent with the hypothesis that they may directly mediate some of the descending excitatory and inhibitory influences on spinal reflex pathways in desynchronized sleep.


1986 ◽  
Vol 55 (2) ◽  
pp. 375-401 ◽  
Author(s):  
T. Drew ◽  
R. Dubuc ◽  
S. Rossignol

Recordings were made from single units in the medullary reticular formation (MRF) between AP-4.2 and AP-12.9 and from the midline to 3.7 mm lateral in chronically prepared, unrestrained cats walking on a treadmill. Recordings were made with rigid microelectrodes held in a microdrive, and reticulospinal neurons were identified by antidromic stimulation of their axons through microwires chronically implanted into the spinal cord at the L2 level. Electromyograms (EMGs) were recorded from flexor and extensor muscles of the fore- and hindlimbs as well as from back and neck muscles. In total, 295 cells were recorded from 40 penetrations in 4 cats; 252 of these cells were recorded from the more medial regions of the reticular formation encompassing the gigantocellular, magnocellular, and lateral tegmental fields; 38.5% of these (97/252) were antidromically identified from the spinal cord. The remaining 43 neurons (43/295) were recorded from a more lateral and ventral position. These medial and ventrolateral groups of neurons differed not only in position but also in aspects of their discharge during locomotion. Rank-ordered raster displays, triggered from the onset of each recorded muscle, were used to correlate neuronal and muscular activity. The discharge rate of 31% of the reticulospinal neurons (30/97) was modulated once or twice in each step cycle and was strictly related to one or more of the recorded EMGs (EMG-related neurons) on the basis of the pattern of discharge. The discharge of 33/97 (34%) of the neurons was modulated at the periodicity of the locomotor rhythm but could not be correlated with any of the recorded EMGs (locomotor-related cells), whereas the remaining 34/97 neurons (35%) were either silent, fired tonically, or were not related to the locomotor pattern (unrelated cells). Of the EMG-related neurons 27% were related to flexor muscles and the remaining 63% to extensor muscle activity. The discharge pattern of all except two of the flexor-related neurons was correlated with hindlimb muscle activity, whereas that of the extensor-related neurons was correlated almost equally with fore- and hindlimb muscles. Correlations were found with muscles lying both ipsilaterally and contralaterally to the site of the recordings. Although the locomotor-related neurons showed no preferential relation with any of the recorded EMGs, a comparison of the depth of modulation of their discharge measured from postevent histograms suggested that more of these cells were related to the forelimb than to the hindlimb.(ABSTRACT TRUNCATED AT 400 WORDS)


2014 ◽  
Vol 111 (7) ◽  
pp. 1507-1518 ◽  
Author(s):  
Mafalda Sousa ◽  
Peter Szucs ◽  
Deolinda Lima ◽  
Paulo Aguiar

Despite the importance and significant clinical impact of understanding information processing in the nociceptive system, the functional properties of neurons in many parts of this system are still unknown. In this work we performed whole cell patch-clamp recording in rat brain stem blocks to characterize the electrophysiological properties of neurons in the dorsal reticular nucleus (DRt), a region known to be involved in pronociceptive modulation. We also compared properties of DRt neurons with those in the adjacent parvicellular reticular nucleus and in neighboring regions outside the reticular formation. We found that neurons in the DRt and parvicellular reticular nucleus had similar electrophysiological properties and exhibited mostly toniclike firing patterns, whereas neurons outside the reticular formation showed a larger diversity of firing patterns. Interestingly, more than one-half of the neurons also showed spontaneous activity. While the general view of the reticular formation, being a loosely associated mesh of groups of neurons with diverse function, and earlier reports suggests more electrophysiological heterogeneity, we showed that this is indeed not the case. Our results indicate that functional difference of neurons in the reticular formation may mostly be determined by their connectivity profiles and not by their intrinsic electrophysiological properties. The dominance of tonic neurons in the DRt supports previous conclusions that these neurons encode stimulus intensity through their firing frequency, while the high prevalence of spontaneous activity most likely shapes nociceptive modulation by this brain stem region.


2021 ◽  
Author(s):  
Atsushi Yoshida ◽  
Misaki Inoue ◽  
Fumihiko Sato ◽  
Yayoi Morita ◽  
Yumi Tsutsumi ◽  
...  

Abstract The supratrigeminal nucleus (Su5) is a key structure for controlling jaw-movements since it receives proprioceptive sensation from jaw-closing muscle spindles (JCMSs) and sends projection to the trigeminal motor nucleus (Mo5). However, the central projection and regulation of JCMS proprioceptive sensation have not been fully understood. Therefore, we aimed to reveal the efferents and afferents of the Su5 by means of neuronal tract tracings. Anterograde tracer injections into the Su5 revealed that the Su5 sent contralateral projections (or bilateral projections with a contralateral predominance) to the Su5, basilar pontine nuclei, pontine reticular nucleus, deep mesencephalic nucleus, superior colliculus, caudo-ventromedial edge of ventral posteromedial thalamic nucleus, parafascicular thalamic nucleus, zona incerta, and lateral hypothalamus, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) to the intertrigeminal region, trigeminal oral subnucleus, dorsal medullary reticular formation, and hypoglossal nucleus as well as the Mo5. Retrograde tracer injections into the Su5 demonstrated that the Su5 received bilateral projections with a contralateral predominance (or contralateral projections) from the primary and secondary somatosensory cortices, granular insular cortex and Su5, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) from the dorsal peduncular cortex, bed nuclei of stria terminalis, central amygdaloid nucleus, lateral hypothalamus, parasubthalamic nucleus, trigeminal mesencephalic nucleus, parabrachial nucleus, juxtatrigeminal region, trigeminal oral and caudal subnuclei, and dorsal medullary reticular formation. These findings suggest that the Su5 receiving JCMS proprioceptive sensation has efferent and afferent connections with multiple brain regions, which are involved in emotional and autonomic functions as well as orofacial motor functions.


1996 ◽  
Vol 76 (1) ◽  
pp. 332-352 ◽  
Author(s):  
C. A. Scudder ◽  
A. K. Moschovakis ◽  
A. B. Karabelas ◽  
S. M. Highstein

1. The intra-axonal recording and horseradish peroxidase injection technique together with spontaneous eye movement monitoring has been employed in alert behaving monkeys to study the discharge pattern and axonal projections of mesencephalic saccade-related long-lead burst neurons (LLBNs). 2. Most of the recovered axons (N = 21) belonged to two classes of neurons. The majority (N = 13) were identified as efferents of the superior colliculus and had circumscribed movement fields typical of collicular saccade-related burst neurons. This discharge pattern, their responses to electrical stimulation of one or both superior colliculi, and their morphological appearance identified them as members of the T class of tectal efferent neurons. 3. Axons of these T cells deployed terminal fields within several saccade-related brain stem areas including the nucleus reticularis tegmenti pontis, which projects to the cerebellum; the nucleus reticularis pontis oralis and caudalis, which contains excitatory premotor burst neurons; the nucleus raphe interpositus, which contains omnipause neurons; the nucleus paragigantocellularis, which contains inhibitory premotor burst neurons, as well as other less differentiated parts of the brain stem reticular formation. 4. The other class of LLBNs (N = 4) had their somata in the medullary reticular formation just lateral to the interstitial nucleus of Cajal. They projected primarily to the raphe nuclei, the medullary reticular formation, and the paramedian reticular nucleus. Discharges were of the directional type with up ON directions (N = 3) and down ON directions (N = 1). 5. Other fibers, which project to pontine and medullary oculomotor structures but whose somata were not recovered (N = 4), illustrate that there are also other types of LLBNs that contribute to the generation and control of saccadic eye movements. 6. Our findings complement previous data about the axonal trajectories of T-type superior colliculus efferents. They also demonstrate the existence of LLBNs located in the mesencephalic reticular formation and their target areas in the brain stem. Implications of these findings for current concepts of oculomotor control are discussed.


1987 ◽  
Vol 66 (4) ◽  
pp. 548-554 ◽  
Author(s):  
Seigo Nagao ◽  
Tsukasa Nishiura ◽  
Hideyuki Kuyama ◽  
Masakazu Suga ◽  
Takenobu Murota

✓ The authors report the results of a study to evaluate the effect of stimulation of the medullary reticular formation on cerebral vasomotor tonus and intracranial pressure (ICP) after the hypothalamic dorsomedial nucleus and midbrain reticular formation were destroyed. Systemic arterial pressure (BP), ICP, and local cerebral blood volume (CBV) were continuously recorded in 32 cats. To assess the changes in the cerebral vasomotor tonus, the vasomotor index defined by the increase in ICP per unit change in BP was calculated. In 29 of the 32 animals, BP, ICP, and CBV increased simultaneously immediately after stimulation. The increase in ICP was not secondary to the increase in BP, because the vasomotor index during stimulation was significantly higher than the vasomotor index after administration of angiotensin II. The vasomotor index was high during stimulation of the area around the nucleus reticularis parvocellularis. In animals with the spinal cord transected at the C-2 vertebral level, ICP increased without a change in BP. These findings indicate that the areas stimulated in the medullary reticular formation play an important role in decreasing cerebral vasomotor tonus. This effect was not influenced by bilateral superior cervical ganglionectomy, indicating that there is an intrinsic neural pathway that regulates cerebral vasomotor tonus directly. In three animals, marked biphasic or progressive increases in ICP up to 100 mm Hg were evoked by stimulation. The reduction of cerebral vasomotor tonus and concomitant vasopressor response induced by stimulation of the medullary reticular formation may be one of the causes of acute brain swelling.


1997 ◽  
Vol 273 (3) ◽  
pp. R896-R904 ◽  
Author(s):  
H. A. Baghdoyan

Microinjecting cholinomimetics into the pontine reticular formation produces a state that resembles natural rapid eye movement (REM) sleep. Evocation of this REM sleeplike states is anatomically site dependent within the pons and is mediated by muscarinic receptors. The cellular and molecular mechanisms underlying cholinergic REM sleep generation and muscarinic receptor subtype involvement remain to be specified. This study tested the hypothesis that muscarinic receptor subtypes are differentially distributed within the oral and caudal divisions of rat pontine reticular nucleus. In vitro receptor autoradiography was used to localize and quantify M1, M2, and M3 binding sites in the pontine reticular formation and in pontine brain stem regions known to regulate REM sleep. M1-M3 binding sites were present in some REM sleep-related nuclei, such as dorsal raphe and locus ceruleus. The pontine reticular formation was found to have a homogeneous distribution of M2 binding sites across its rostral to caudal extent, indicating that anatomic specificity of cholinergic REM sleep induction cannot be accounted for by a differential density of muscarinic receptors.


1990 ◽  
Vol 63 (5) ◽  
pp. 1118-1127 ◽  
Author(s):  
L. Villanueva ◽  
K. D. Cliffer ◽  
L. S. Sorkin ◽  
D. Le Bars ◽  
W. D. Willis

1. Recordings were made in anesthetized monkeys from neurons in the medullary reticular formation (MRF) caudal to the obex. Responses of 19 MRF neurons to mechanical, thermal, and/or electrical stimulation were examined. MRF neurons exhibited convergence of nociceptive cutaneous inputs from widespread areas of the body and face. 2. MRF neurons exhibited low levels of background activity. Background activity increased after periods of intense cutaneous mechanical or thermal stimulation. Nearly all MRF neurons tested failed to respond to heterosensory stimuli (flashes, whistle sounds), and none responded to joint movements. 3. MRF neurons were excited by and encoded the intensity of noxious mechanical stimulation. Responses to stimuli on contralateral limbs were greater than those to stimuli on ipsilateral limbs. Responses were greater to stimuli on the forelimbs than to stimuli on the hindlimbs. 4. MRF neurons responded to noxious thermal stimulation (51 degrees C) of widespread areas of the body. Mean responses from stimulation at different locations were generally parallel to those for noxious mechanical stimulation. Responses increased with intensity of noxious thermal stimulation (45-50 degrees C). 5. MRF neurons responded with one or two peaks of activation to percutaneous electrical stimulation applied to the limbs, the face, or the tail. The differences in latency of responses to stimulating two locations along the tail suggested that activity was elicited by activation of peripheral fibers with a mean conduction velocity in the A delta range. Stimulation of the contralateral hindlimb elicited greater responses, with lower thresholds and shorter latencies, than did stimulation of the ipsilateral hindlimb. 6. Electrophysiological properties of monkey MRF neurons resembled those of neurons in the medullary subnucleus reticularis dorsalis (SRD) in the rat. Neurons in the caudal medullary reticular formation could play a role in processing nociceptive information. Convergence of nociceptive cutaneous input from widespread areas of the body suggests that MRF neurons may contribute to autonomic, affective, attentional, and/or sensory-motor processes related to pain.


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