scholarly journals Brainstem Neurons that Command Left/Right Locomotor Asymmetries

2019 ◽  
Author(s):  
Jared M. Cregg ◽  
Roberto Leiras ◽  
Alexia Montalant ◽  
Ian R. Wickersham ◽  
Ole Kiehn

Descending command neurons instruct spinal networks to execute basic locomotor functions, such as which gait and what speed. The command functions for gait and speed are symmetric, implying that a separate unknown system directs asymmetric movements—the ability to move left or right. Here we report the discovery that Chx10-lineage reticulospinal neurons act to control the direction of locomotor movements in mammals. Chx10 neurons exhibit ipsilateral projection, and can decrease spinal limb-based locomotor activity ipsilaterally. This circuit mechanism acts as the basis for left or right locomotor movements in freely moving animals: selective unilateral activation of Chx10 neurons causes ipsilateral movements whereas inhibition causes contralateral movements. Spontaneous forward locomotion is thus transformed into an ipsilateral movement by braking locomotion on the ipsilateral side. We identify sensorimotor brain regions that project onto Chx10 reticulospinal neurons, and demonstrate that their unilateral activation can impart left/right directional commands. Together these data identify the descending motor system which commands left/right locomotor asymmetries in mammals.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jacek Wróbel ◽  
Władysław Średniawa ◽  
Gabriela Jurkiewicz ◽  
Jarosław Żygierewicz ◽  
Daniel K. Wójcik ◽  
...  

Abstract Changes in oscillatory activity are widely reported after subanesthetic ketamine, however their mechanisms of generation are unclear. Here, we tested the hypothesis that nasal respiration underlies the emergence of high-frequency oscillations (130–180 Hz, HFO) and behavioral activation after ketamine in freely moving rats. We found ketamine 20 mg/kg provoked “fast” theta sniffing in rodents which correlated with increased locomotor activity and HFO power in the OB. Bursts of ketamine-dependent HFO were coupled to “fast” theta frequency sniffing. Theta coupling of HFO bursts were also found in the prefrontal cortex and ventral striatum which, although of smaller amplitude, were coherent with OB activity. Haloperidol 1 mg/kg pretreatment prevented ketamine-dependent increases in fast sniffing and instead HFO coupling to slower basal respiration. Consistent with ketamine-dependent HFO being driven by nasal respiration, unilateral naris blockade led to an ipsilateral reduction in ketamine-dependent HFO power compared to the control side. Bilateral nares blockade reduced ketamine-induced hyperactivity and HFO power and frequency. These findings suggest that nasal airflow entrains ketamine-dependent HFO in diverse brain regions, and that the OB plays an important role in the broadcast of this rhythm.


1989 ◽  
Vol 9 (5) ◽  
pp. 579-588 ◽  
Author(s):  
Astrid Nehlig ◽  
Anne Pereira de Vasconcelos ◽  
Sylvette Boyet

The postnatal changes in local cerebral blood flow in freely moving rats were measured by means of the quantitative autoradiographic [14C]iodoantipyrine method. The animals were studied at 10, 14, 17, 21, and 35 days and at the adult stage. At 10 days after birth, rates of blood flow were very low and quite homogeneous in most cerebral structures except in a few posterior areas. From these relatively uniform levels, values of local cerebral blood flow rose notably to reach a peak at 17 days in all brain regions studied. Rates of blood flow decreased between 17 and 21 days after birth and then increased from weaning time to reach the known characteristic distribution of the adult rat. The postnatal evolution of local cerebral blood flow in the rat is in good agreement with previous studies in other species such as dog and humans that also show higher rates of cerebral blood flow and glucose utilization at immature stages. However, in the rat, local cerebral blood flow and local cerebral glucose utilization are not coupled over the whole postnatal period studied, since blood flow rates reach peak values at 17 days whereas glucose utilization remains still quite low at that stage. The high rate of cerebral blood flow in the 17-day-old rat may reflect the energetic and biosynthetic needs of the actively developing brain that are completed by the summation of glucose and ketone body utilization.


2003 ◽  
Vol 90 (2) ◽  
pp. 1071-1083 ◽  
Author(s):  
Philippe A. Chouinard ◽  
Ysbrand D. Van Der Werf ◽  
Gabriel Leonard ◽  
Tomás Paus

Our study uses the combined transcranial magnetic stimulation/positron emission tomography (TMS/PET) method for elucidating neural connectivity of the human motor system. We first altered motor excitability by applying low-frequency repetitive TMS over two cortical motor regions in separate experiments: the dorsal premotor and primary motor cortices. We then assessed the consequences of modulating motor excitability by applying single-pulse TMS over the primary motor cortex and measuring: 1) muscle responses with electromyography and 2) cerebral blood flow with PET. Low-frequency repetitive stimulation reduced muscle responses to a similar degree in both experiments. To map networks of brain regions in which activity changes reflected modulation of motor excitability, we generated t-statistical maps of correlations between reductions in muscle response and differences in cerebral blood flow. Low-frequency repetitive stimulation altered neural activity differently in both experiments. Neural modulation occurred in multiple brain regions after dorsal premotor cortex stimulation; these included motor regions in the frontal cortex as well as more associational regions in the parietal and prefrontal cortices. In contrast, neural modulation occurred in a smaller number of brain regions after primary motor cortex stimulation, many of these confined to the motor system. These findings are consistent with the known differences between the dorsal premotor and primary motor cortices in the extent of cortico-cortical anatomical connectivity in the monkey.


2020 ◽  
Author(s):  
James A. Frank ◽  
Marc-Joseph Antonini ◽  
Po-Han Chiang ◽  
Andres Canales ◽  
David B. Konrad ◽  
...  

ABSTRACTTo reversibly manipulate neural circuits with increased spatial and temporal control, photoswitchable ligands can add an optical switch to a target receptor or signaling cascade. This approach, termed photopharmacology, has been enabling to molecular neuroscience, however, its application to behavioral experiments has been impeded by a lack of integrated hardware capable of delivering both light and compounds to deep brain regions in moving subjects. Here, we devise a hybrid photochemical genetic approach to target neurons using a photoswitchable agonist of capsaicin receptor (TRPV1), red-AzCA-4. Using the thermal drawing process we created multifunctional fibers that can deliver viruses, photoswitchable ligands, and light to deep brain regions in awake, freely moving mice. We implanted our fibers into the ventral tegmental area (VTA), a midbrain hub of the mesolimbic pathway, and used them to deliver a transgene coding for TRPV1. This sensitized excitatory VTA neurons to red-AzCA-4, and allowed us to optically control conditioned place preference using a mammalian ion-channel, thus extending applications of photopharmacology to behavioral experiments. Applied to endogenous receptors, our approach may accelerate studies of molecular mechanisms underlying animal behavior.


2021 ◽  
Vol 13 ◽  
Author(s):  
Estibaliz Etxeberria-Rekalde ◽  
Saioa Alzola-Aldamizetxebarria ◽  
Stefanie Flunkert ◽  
Isabella Hable ◽  
Magdalena Daurer ◽  
...  

Huntington’s disease (HD) is caused by an expansion of CAG triplets in the huntingtin gene, leading to severe neuropathological changes that result in a devasting and lethal phenotype. Neurodegeneration in HD begins in the striatum and spreads to other brain regions such as cortex and hippocampus, causing motor and cognitive dysfunctions. To understand the signaling pathways involved in HD, animal models that mimic the human pathology are used. The R6/2 mouse as model of HD was already shown to present major neuropathological changes in the caudate putamen and other brain regions, but recently established biomarkers in HD patients were yet not analyzed in these mice. We therefore performed an in-depth analysis of R6/2 mice to establish new and highly translational readouts focusing on Ctip2 as biological marker for motor system-related neurons and translocator protein (TSPO) as a promising readout for early neuroinflammation. Our results validate already shown pathologies like mutant huntingtin aggregates, ubiquitination, and brain atrophy, but also provide evidence for decreased tyrosine hydroxylase and Ctip2 levels as indicators of a disturbed motor system, while vesicular acetyl choline transporter levels as marker for the cholinergic system barely change. Additionally, increased astrocytosis and activated microglia were observed by GFAP, Iba1 and TSPO labeling, illustrating, that TSPO is a more sensitive marker for early neuroinflammation compared to GFAP and Iba1. Our results thus demonstrate a high sensitivity and translational value of Ctip2 and TSPO as new marker for the preclinical evaluation of new compounds in the R6/2 mouse model of HD.


2019 ◽  
Author(s):  
Jonathan J. Cannon ◽  
Aniruddh D. Patel

AbstractBeat perception is central to music cognition. The motor system is involved in beat perception, even in the absence of movement, yet current frameworks for modeling beat perception do not strongly engage with the motor system’s neurocomputational properties. We believe fundamental progress on modeling beat perception requires a synthesis between cognitive science and motor neuroscience, yielding predictions to guide research. Success on this front would be a landmark in the study of how “embodied cognition” is implemented in brain activity. We illustrate this approach by proposing specific roles for two key motor brain structures (the supplementary motor area, and the dorsal striatum of the basal ganglia) in covert beat maintenance, building on current research on their role in actual movement.Highlights⍰Components of the brain’s motor system are activated by the perception of a musical beat, even in the absence of movement, and may play an important role in beat-based temporal prediction.⍰Two key brain regions involved in movement, the supplementary motor area and dorsal striatum, have neurocomputational properties that lend themselves to beat perception.⍰In supplementary motor area, neural firing rates represent the phase of cyclic sensorimotor processes.⍰Supplementary motor area’s involvement in perceptual suppression of self-generated sounds suggests that it could play a broader role in informing auditory expectations.⍰Dorsal striatum plays a central role in initiating and sequencing units of movement, and may serve similar functions in structuring beat-based temporal anticipation.


1982 ◽  
Vol 242 (3) ◽  
pp. E164-E170
Author(s):  
P. C. Leung ◽  
D. I. Whitmoyer ◽  
C. H. Sawyer

In both ovariectomized (OVX) and steroid-primed OVX freely moving rats, attempts were made to correlate the effects of intraventricular norepinephrine (NE) on multiunit activity (MUA) of different brain regions with NE-induced alterations in blood LH levels. MUA-recording electrodes were implanted in the diagonal band of Broca (DBB), medial preoptic area (MPOA), arcuate nucleus (ARC) and/or ventromedial hypothalamic nucleus (VMH). Steroid priming included 50 micrograms estradiol benzoate (EB) and 25 mg progesterone (P) 3 days prior to experiment. The unanesthetized animals were bled via indwelling atrial cannulas before and after intraventricular infusion of NE (10 micrograms in 2 microliters over 2 min). In OVX-primed rats NE lengthened the interval between episodic LH peaks and decreased mean blood LH levels. In contrast, in OVX-EBP-primed rats, NE stimulated an LH surge. Concurrent recording of MUA revealed that, in OVX-unprimed rats, NE dramatically depressed MUA in both DBB-MPO and ARC-VMH neurons. However, in OVX-EBP-primed rats, while still markedly inhibiting ARC-VMH units, NE failed to depress MUA recorded in DBB-MPO sites (some units were actually excited by NE), perhaps reflecting the higher ratio of LHRH neurons/inhibitory neurons in DBB-MPO.


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