scholarly journals Cholinergic Regulation of the Posterior Medial Thalamic Nucleus

2006 ◽  
Vol 96 (5) ◽  
pp. 2265-2273 ◽  
Author(s):  
Radi Masri ◽  
Jason C. Trageser ◽  
Tatiana Bezdudnaya ◽  
Ying Li ◽  
Asaf Keller

We previously showed that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incertothalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brain stem cholinergic system, which regulates sleep–wake cycles and states of vigilance. We demonstrate that cholinergic inputs facilitate POm responses to vibrissae stimulation. Activation of the cholinergic system by stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and the pedunculopontine tegmental) or by tail pinch significantly increased the magnitude of POm responses to vibrissae stimulation. Microiontophoresis of the muscarinic receptor agonist carbachol enhanced POm responses to vibrissae stimulation. Application of carbachol to an in vitro slice preparation reduced the frequency but not the amplitude of miniature inhibitory postsynaptic currents, indicating a presynaptic site of action for carbachol. We conclude that the cholinergic system facilitates POm responses by suppressing GABAergic inputs from ZI. We propose the state-dependent gating hypothesis, which asserts that differing behavioral states, regulated by the brain stem cholinergic system, modulate the flow of information through POm.

2006 ◽  
Vol 96 (3) ◽  
pp. 1456-1463 ◽  
Author(s):  
Jason C. Trageser ◽  
Kathryn A. Burke ◽  
Radi Masri ◽  
Ying Li ◽  
Larisa Sellers ◽  
...  

We have previously shown that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incerto-thalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that the cholinergic reticular activating system, implicated in regulating states of arousal, modulates ZI activity. We show that stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and pedunculopontine tegmental) results in suppression of spontaneous firing of ZI neurons. Iontophoretic application of the cholinergic agonist carbachol to ZI neurons suppresses both their spontaneous firing and their vibrissae-evoked responses. We also found that carbachol application to an in vitro slice preparation suppresses spontaneous firing of neurons in the ventral sector of ZI (ZIv). Finally, we demonstrate that the majority of ZIv neurons contain parvalbumin and project to POm. Based on these results, we present the state-dependent gating hypothesis, which states that differing behavioral states—regulated by the brain stem cholinergic system—modulate ZI activity, thereby regulating the response properties of higher-order nuclei such as POm.


2019 ◽  
Vol 122 (5) ◽  
pp. 2061-2075
Author(s):  
Omer Tsur ◽  
Yana Khrapunsky ◽  
Rony Azouz

The rodent’s vibrissal system is a useful model system for studying sensorimotor integration in perception. This integration determines the way in which sensory information is acquired by sensory organs and the motor commands that control them. The initial instance of sensorimotor integration in the whisker somatosensory system is implemented in the brain stem loop and may be essential to the way rodents explore and sense their environment. To examine the nature of these sensorimotor interactions, we recorded from lightly anesthetized rats in vivo and brain stem slices in vitro and isolated specific parts of this loop. We found that motor feedback to the vibrissal pad serves as a dynamic gain controller that controls the response of first-order sensory neurons by increasing and decreasing sensitivity to lower and higher tactile stimulus magnitudes, respectively. This delicate mechanism is mediated through tactile stimulus magnitude-dependent motor feedback. Conversely, tactile inputs affect the motor whisking output through influences on the rhythmic whisking circuitry, thus changing whisking kinetics. Similarly, tactile influences also modify the whisking amplitude through synaptic and intrinsic neuronal interaction in the facial nucleus, resulting in facilitation or suppression of whisking amplitude. These results point to the vast range of mechanisms underlying sensorimotor integration in the brain stem loop. NEW & NOTEWORTHY Sensorimotor integration is a process in which sensory and motor information is combined to control the flow of sensory information, as well as to adjust the motor system output. We found in the rodent’s whisker somatosensory system mutual influences between tactile inputs and motor output, in which motor neurons control the flow of sensory information depending on their magnitude. Conversely, sensory information can control the magnitude and kinetics of whisker movement.


2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.


1993 ◽  
Vol 70 (6) ◽  
pp. 2241-2250 ◽  
Author(s):  
M. K. Floeter ◽  
A. Lev-Tov

1. The excitation of lumbar motoneurons by reticulospinal axons traveling in the medial longitudinal fasciculus (MLF) was investigated in the newborn rat using intracellular recordings from lumbar motoneurons in an in vitro preparation of the brain stem and spinal cord. The tracer DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine) was introduced into the MLF of 6-day-old littermate rats that had been fixed with paraformaldehyde to evaluate the anatomic extent of this developing pathway. 2. Fibers labeled from the MLF by DiI were present in the cervical ventral and lateral white matter and a smaller number of labeled fibers extended to the lumbar enlargement. Patches of sparse terminal labeling were seen in the lumbar ventral gray. 3. In the in vitro preparation of the brain stem and spinal cord, MLF stimulation excited motoneurons through long-latency pathways in most motoneurons and through both short-(< 40 ms) and long-latency connections in 16 of 40 motoneurons studied. Short- and longer-latency components of the excitatory response were evaluated using mephenesin to reduce activity in polysynaptic pathways. 4. Paired-pulse stimulation of the MLF revealed a modest temporal facilitation of the short-latency excitatory postsynaptic potential (EPSP) at short interstimulus intervals (20–200 ms). Trains of stimulation at longer interstimulus intervals (1–30 s) resulted in a depression of EPSP amplitude. The time course of the synaptic depression was compared with that found in EPSPs resulting from paired-pulse stimulation of the dorsal root and found to be comparable. 5. The short-latency MLF EPSP was reversibly blocked by 6-cyano-7-nitroquinoxaline (CNQX), an antagonist of non-N-methyl-D-aspartate glutamate receptors, with a small CNQX-resistant component. Longer-latency components of the MLF EPSP were also blocked by CNQX, and some late components of the PSP were sensitive to strychnine. MLF activation of multiple polysynaptic pathways in the spinal cord is discussed.


2006 ◽  
Vol 96 (4) ◽  
pp. 2042-2055 ◽  
Author(s):  
James F. Einum ◽  
James T. Buchanan

An in vitro preparation of the nervous system of the lamprey, a lower vertebrate, was used to characterize the properties of spinal neurons with axons projecting to the brain stem [i.e., spinobulbar (SB) neurons)]. To identify SB neurons, extracellular electrodes on each side of the spinal cord near the obex recorded the axonal spikes of neurons impaled with sharp intracellular microelectrodes in the rostral spinal cord. The ascending spinal neurons ( n = 144) included those with ipsilateral (iSB) (63/144), contralateral (cSB) (77/144), or bilateral (bSB) (4/144) axonal projections to the brain stem. Intracellular injection of biocytin revealed that the SB neurons had small- to medium-size somata and most had dendrites confined to the ipsilateral side of the cord, although about half of the cSB neurons also had contralateral dendrites. Most SB neurons had multiple axonal branches including descending axons. Electrophysiologically, the SB neurons were similar to other lamprey spinal neurons, firing spikes throughout long depolarizing pulses with some spike-frequency adaptation. Paired intracellular recordings between SB and reticulospinal (RS) neurons revealed that SB neurons made either excitatory or inhibitory synapses on RS neurons and the SB neurons received excitatory input from RS neurons. Mutual excitation and feedback inhibition between pairs of RS and SB neurons were observed. The SB neurons also received excitatory inputs from primary mechanosensory neurons (dorsal cells), and these same SB neurons were rhythmically active during fictive swimming, indicating that SB neurons convey both sensory and locomotor network information to the brain stem.


2010 ◽  
Vol 103 (2) ◽  
pp. 648-658 ◽  
Author(s):  
Heather J. Yu ◽  
Ayako Yamaguchi

Serotonin initiates various rhythmic behaviors in vertebrates. Previously we have shown that serotonergic neurons innervate the central vocal pathway in the African clawed frog ( Xenopus laevis ). We also discovered that exogenous serotonin applied to isolated brains in vitro activates fictive vocalizations by activating 5-HT2C-like receptors. In this study, we examined the location of 5-HT2C-like receptors and determined whether endogenously released serotonin also initiates vocalizations by activating 5-HT2C-like receptors in male Xenopus brains. To this end, we first identified the specific location of 5-HT2C-like receptors using immunohistochemistry. We next examined which of the populations of neurons that express 5-HT2C-like receptors are functionally relevant for initiating fictive vocalizations by applying a 5-HT2C receptor agonist to brains transected at various levels. Of four populations of immunopositive neurons, we showed that 5-HT2C-like receptors located in two areas of the brain stem vocal circuit, the raphe nucleus and motor nucleus IX-X, initiate fictive vocalizations. We next showed that endogenous serotonin can also activate fictive vocalizations by increasing the extracellular concentration of endogenous serotonin using a selective serotonin reuptake inhibitor (SSRI). The SSRI-induced vocal initiation is also mediated by activation of 5-HT2C-like receptors because blockade of these receptors prevents fictive vocalization. The results suggest that in vivo release of serotonin initiates male vocalizations by activating 5-HT2C-like receptors in the brain stem vocal nuclei.


2005 ◽  
Vol 93 (4) ◽  
pp. 2127-2141 ◽  
Author(s):  
Frédéric Brocard ◽  
Cédric Bardy ◽  
Réjean Dubuc

Substance P initiates locomotion when injected in the brain stem of mammals. This study examined the possible role of this peptide on the supraspinal locomotor command system in lampreys. Substance P was bath applied or locally injected into an in vitro isolated brain stem, and the effects of the drug were examined on reticulospinal cells and on the occurrence of swimming in a semi-intact preparation. Bath applications of substance P induced sustained depolarizations occurring rhythmically in intracellularly recorded reticulospinal cells. Spiking activity was superimposed on the depolarizations and swimming was induced. The sustained depolarizations were abolished by tetrodotoxin, and substance P did not affect the membrane resistance of reticulospinal cells nor their firing properties, suggesting that it did not directly effect reticulospinal cells. To establish where the effects were exerted, successive lesions of the brain stem were made as well as local applications of the drug in the brain stem. Removing the mesencephalon abolished the sustained depolarizations, whereas large ejections of the drug in the mesencephalon excited reticulospinal cells and elicited bouts of swimming. More local injections into the mesencephalic locomotor region (MLR) also elicited swimming. After an injection of substance P, the current threshold needed to induce locomotion by MLR stimulation was decreased, and the size of the postsynaptic responses of reticulospinal cells to MLR stimulation was increased. Substance P also reduced the frequency of miniature spontaneous postsynaptic currents in reticulospinal cells. Taken together, these results suggest that substance P plays a neuromodulatory role on the brain stem locomotor networks of lampreys.


2005 ◽  
Vol 93 (2) ◽  
pp. 1042-1054 ◽  
Author(s):  
Michael Ariel

Responses of separate regions of rat cerebellar cortex (Cb) to inferior olive (IO) stimulation occur with the same latency despite large differences in climbing fiber (CF) lengths. Here, the olivocerebellar path of turtle was studied because its Cb is an unfoliated sheet on which measurements of latency and CF length can be made directly across its entire surface in vitro. During extracellular DC recordings at a given Cb position below the molecular layer, IO stimulation evoked a large negative field potential with a half-width duration of ∼6.5 ms. On this response were smaller oscillations similar to complex spikes. The stimulating electrode was moved to map the IO and the CF path from the brain stem to the Cb. The contralateral brain stem region that evoked these responses was tightly circumscribed within the medulla, lateral and deep to the obex. This response remained when the brain stem was bathed in solutions that blocked synaptic transmission. The Cb response to IO stimulation had a peak latency of ∼10 ms that was not dependent on the position of the recording electrode across the entire 8-mm rostrocaudal length of the Cb. However, for a constant Cb recording position, moving the stimulation across the midline to the ipsilateral brain stem and along the lateral wall of the fourth ventricle toward the peduncle did shorten the response latency. Therefore a synchronous Cb response to CF stimulation seems to be caused by changes in its conduction velocity within the entire cerebellar cortex but not within the brain stem.


1998 ◽  
Vol 85 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Rebecca A. Johnson ◽  
Stephen M. Johnson ◽  
Gordon S. Mitchell

An in vitro brain stem preparation from adult turtles was used to determine effects of dopamine (DA) and norepinephrine (NE) on the pattern of respiratory motor output recorded from hypoglossal nerve roots (XII). Bath-applied DA (10–200 μM) increased the frequency of respiratory bursts (peaks) from 0.9 ± 0.2 to 2.4 ± 0.3 (SE) peaks/min, resulting in a 99 ± 9% increase in neural minute activity. R[+]-SCH-23390 (10 μM, D1 antagonist) and eticlopride (20 μM, D2 antagonist) attenuated the DA-mediated increase in peak frequency by 52 and 59%, respectively. On the other hand, the DA-receptor agonists apomorphine (D1, D2), quinelorane (D2), and SKF-38393 (D1) had no effect on peak frequency. Prazosin, an α1-adrenergic antagonist (250 nM) abolished the DA-mediated frequency increase. Although NE (10–200 μM) and phenylephrine (10–200 μM, α1-adrenergic agonist) increased peak frequency from 0.5 ± 0.1 to 1.2 ± 0.3 peaks/min and from 0.6 ± 0.1 to 1.0 ± 0.2 peaks/min, respectively, these effects were not as large as that with DA alone. The data suggest that both dopaminergic and adrenergic receptor activation in the brain stem increase respiratory frequency in turtles, but the DA receptor-mediated increase is dependent on coactivation of α1-adrenergic receptors.


2001 ◽  
Vol 85 (4) ◽  
pp. 1489-1497 ◽  
Author(s):  
Manuel A. Castro-Alamancos ◽  
Maria E. Calcagnotto

The thalamus is the principal relay station of sensory information to the neocortex. In return, the neocortex sends a massive feedback projection back to the thalamus. The thalamus also receives neuromodulatory inputs from the brain stem reticular formation, which is vigorously activated during arousal. We investigated the effects of two neuromodulators, acetylcholine and norepinephrine, on corticothalamic responses in vitro and in vivo. Results from rodent slices in vitro showed that acetylcholine and norepinephrine depress the efficacy of corticothalamic synapses while enhancing their frequency-dependent facilitation. This produces a stronger depression of low-frequency responses than of high-frequency responses. The effects of acetylcholine and norepinephrine were mimicked by muscarinic and α2-adrenergic receptor agonists and blocked by muscarinic and α-adrenergic antagonists, respectively. Stimulation of the brain stem reticular formation in vivo also strongly depressed corticothalamic responses. The suppression was very strong for low-frequency responses, which do not produce synaptic facilitation, but absent for high-frequency corticothalamic responses. As in vitro, application of muscarinic and α-adrenergic antagonists into the thalamus in vivo abolished the suppression of corticothalamic responses induced by stimulating the reticular formation. In conclusion, cholinergic and noradrenergic activation during arousal high-pass filters corticothalamic activity. Thus, during arousal only high-frequency inputs from the neocortex are allowed to reach the thalamus. Neuromodulators acting on corticothalamic synapses gate the flow of cortical activity to the thalamus as dictated by behavioral state.


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