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The locus coeruleus is involved in processing information regarding environmental context (A) LVST-neurons labelled via CTB-647 injection into the lumbar spinal cord and sections stained with antityrosine hydroxylase. Higher magnification images (middle and right) show apposition of tyrosine hydroxylase positive enlargements in the vicinity of LVST-neurons. (B) Experimental procedure to test effect of noradrenergic neurotoxin DSP4 on responses to lateral perturbations. (C) Comparison of peak EMG amplitudes in TA after perturbation in control animals in high and low walled conditions. (D) Comparison of peak EMG amplitudes in TA muscle after perturbation in animals following DSP4 injection in high and low walled conditions. (E) Experimental procedure for selective labelling of noradrenergic neurons in the locus coeruleus using the PRSx8 promoter. (F) Tyrosine hydroxylase immunostaining at site of injection of AAV described in (E). (G) GFP labelling and (H) merge of same site shown in (F). (I) Proportion of TH-positive neurons in the locus coeruleus that express GFP following AAV injection. (J) Proportion of TH-negative neurons expressing GFP. (K) Experimental strategy for blocking synaptic transmission from neurons in the locus coeruleus. (L) Bilateral targeting of TeLC-GFP to the locus coeruleus. (M) Higher magnification of image in (L). (N) Peak EMG responses of TA muscle in response to perturbations in high or low walled conditions in animals expressing GFP in the locus coeruleus. (O) Peak EMG responses of TA muscle in response to perturbations in high or low walled conditions in animals expressing GFP-TeLC in the locus coeruleus.
Source publication
Animals possess a remarkable ability to quickly and accurately respond to challenges to their balance and posture. Postural corrections are the implementation of a motor act by the nervous system that counteracts a perturbation and returns the body to a stable state. These corrections must respect both the current position of the limbs and trunk, a...
Contexts in source publication
Context 1
... first looked at noradrenergic input to the LVN by examining tyrosine hydroxylase (TH; which is present in noradrenergic and dopaminergic neurons) immunostaining in the LVN. We observed extensive TH labelling in axons throughout the LVN, in close apposition to LVST-neurons labelled via cholera toxin beta (CTb) injected into the lumbar spinal cord (Figure 4A), suggesting noradrenergic input to the LVN as has been shown previously in rats (Schuerger & Balaban 1993). ...
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... we examined whether pharmacological disruption of noradrenergic neurons would affect the EMG response to a perturbation in different environmental conditions. Again, we systemically administered DSP4 to disrupt noradrenergic neurotransmission ( Figure 4B). In the TA muscle, before administration of DSP4, EMG peak amplitudes were greater in low walled (34.3±13.9 ...
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... systemic administration of DSP4, similar peak EMG amplitudes were recorded in mouse hind limb muscles in the high (32.2±6.4 mV) and low (35.3±14.6 mV) walled conditions following perturbation (p=0.73; Figure 4B-D). These results are consistent with a potential role for noradrenergic signalling in setting the gain of a postural response. ...
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... took advantage of a previously reported noradrenergic selective promoter PRSx8, a synthetic promotor containing Phox2B binding motifs (Hwang et al 2001), which we cloned and packaged into an AAV. We first assessed the specificity of the PRSx8 promoter in an AAV by placing it upstream of a GFP reporter which was packaged into an AAV-DJ capsid ( Figure 4E). Stereotaxic injection of this vector into the LC of wildtype mice resulted in 61.6%+/-8.9% of LC neurons expressing GFP ( Figure 4F-I). ...
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... first assessed the specificity of the PRSx8 promoter in an AAV by placing it upstream of a GFP reporter which was packaged into an AAV-DJ capsid ( Figure 4E). Stereotaxic injection of this vector into the LC of wildtype mice resulted in 61.6%+/-8.9% of LC neurons expressing GFP ( Figure 4F-I). In contrast, 20.3+/-8.6% of GFP-positive neurons did not express tyrosine hydroxylase (though this could represent neurons expressing low levels of tyrosine hydroxylase) ( Figure 4J). ...
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... injection of this vector into the LC of wildtype mice resulted in 61.6%+/-8.9% of LC neurons expressing GFP ( Figure 4F-I). In contrast, 20.3+/-8.6% of GFP-positive neurons did not express tyrosine hydroxylase (though this could represent neurons expressing low levels of tyrosine hydroxylase) ( Figure 4J). ...
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... next packaged an AAV expressing cre recombinase under control of the PRSx8 promoter and coinjected this along with an AAV containing a cre-conditional tetanus toxin light chain fused to GFP, or GFP alone ( Figure 4K)(Murray et al 2011). Tetanus toxin light chain prevents synaptic transmission through disruption of vesicle docking. ...
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... toxin light chain prevents synaptic transmission through disruption of vesicle docking. In these experimental conditions synaptic transmission is selectively blocked from noradrenergic neurons in the locus coeruleus only ( Figure 4K,L,M). Control animals expressing GFP in the locus coeruleus showed an increased EMG amplitude in response to perturbation in low walled vs. high walled conditions in the TA muscle (high mean max amplitude 38.8±4.4mV; ...
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... mean max amplitude 66.5±9.7; n=5 mice; p=0.048 Figure 4N). However, blockade of synaptic transmission resulted in highly similar EMG responses in high and low walled conditions (high mean max. ...
