Changes in brain functional activation during resting and locomotor states after unilateral nigrostriatal damage in rats

Abstract

To evaluate functional neuronal compensation after partial damage to the nigrostriatal system, we lesioned rats unilaterally in the striatum with 6-hydroxydopamine. Five weeks later, cerebral perfusion was mapped at rest or during treadmill walking using [(14)C]-iodoantipyrine. Regional CBF-related tissue radioactivity (CBF-TR) was quantified by autoradiography and analyzed by statistical parametric mapping and region-of- interest analysis. Lesions were confirmed by tyrosine hydroxylase immunohistochemistry and changes in rotational locomotor activity. Functional compensations were bilateral and differed at rest and during treadmill walking. Consistent with the classic view of striatopallidal connections, CBF-TR of lesioned compared to sham-lesioned rats increased in the ipsilateral subthalamic nucleus (STN) and internal globus pallidus, and decreased in the striatum and external globus pallidus. Contrary to the classic view, CBF-TR increased in the ipsilateral ventral lateral, ventral anterior thalamus and motor cortex, as well as in the central medial thalamus, midline cerebellum, and contralateral STN. During walking, perfusion decreased in lesioned compared to sham-lesioned rats across the ipsilateral striato-pallidal-thalamic-cortical motor circuit. Compensatory increases were seen bilaterally in the ventromedial thalamus and red nucleus, in the contralateral STN, anterior substantia nigra, subiculum, motor cortex, and in midline cerebellum. Enhanced recruitment of associative sensory areas was noted cortically and subcortically. Future models of compensatory changes after nigrostriatal damage need to address the effects of increased neural activity by residual dopaminergic neurons, interhemispheric interactions and differences between resting and locomotor states. Identification of sites at which functional compensation occurs may define useful future targets for neurorehabilitative or neurorestorative interventions in Parkinson's disease.

Exposure to inhomogeneous static magnetic field ceases mechanical allodynia in neuropathic pain in mice

“…In principle, these motion-induced currents may stimulate peripheral nerves if the time derivative of the flux density is larger than 40 T/s [Gandhi and Chen, 1999;Schenck, 2000;Formica and Silvestri, 2004;Bencsik et al, 2007;Tomasi and Wang, 2007]. Taking the measured physical parameters of the device into account and calculating with the estimated value of 0.5 m/s for the motion velocity of the animals within the cage (according to the rigorously precise measurements of Yang et al [2007] the normal walking speed of a mouse is around 0.03 m/ s), the time derivative of the flux density for our iSMF apparatus cannot be larger than 24 T/s. If we then continue this calculation by using the value of maximum induced current estimated for a human phantom [Crozier and Liu, 2005] with a size conversion from human to mouse according to the inverse-square law [Dawson et al, 2003], it turns out that the maximum induced current in a mouse in our iSMF can be around 0.04 mA/m 2 .…”

Detection of Visual Activation in the Rat Brain Using 2-deoxy-2-[18F]fluoro-d-glucose and Statistical Parametric Mapping (SPM)

“…Few studies have used SPM techniques in rats with different imaging modalities: autoradiographic iodoantipyrine [30][31][32][33][34], fMRI [35][36][37][38][39][40], and FDG-PET [20,41,42]. Two PET studies used a standardization according to a custom digital template matched to a highresolution microMRI image in Paxinos orientation [41,42].…”

Brain maps on the go: Functional imaging during motor challenge in animals

“…Although quadrupedal gait may in principle involve activation of different neural circuits than bipedal gait, our previous work mapping CBF during treadmill walking in normal, nonlesioned rats showed activation during the task of motor circuits (primary motor cortex, dorsolateral striatum, ventrolateral thalamus, midline cerebellum), in primary somatosensory cortex mapping the forelimbs, hindlimbs and trunk, as well as in secondary visual cortex (5,9,29,30). These results in rats concur with work in humans that demonstrates during walking increases of regional cerebral blood flow in the supplementary motor area, medial primary sensorimotor area, the striatum, visual cortex and the cerebellar vermis using single photon emission computed tomography (62,63).…”

“…For instance, Lewis et al (1) and others (2)(3)(4)(5) have highlighted the dominance of the cerebellar-thalamic-cortical circuit during the performance of externally guided motor movement, and contrasted this with the dominance of the basal ganglia-thalamic-cortical circuit during the performance of internally guided motor movements. Past studies (6)(7)(8), as well as our own work (9) have highlighted the fact, that in response to brain lesions, there is both increased reliance on remaining neurons within damaged circuits, as well as new recruitment of alternate circuits. Imaging can also provide information about neurotransmitter release within specific circuits, and has been extensively developed for the study of dopamine transmission at D2 receptors.…”

“…Such activated brain states may serve to accentuate differences that only manifest partially while a subject is in the resting state. For instance, brain mapping performed during motor challenges has been performed in early PD (15)(16)(17) and in animal models of PD (9), and here has shown utility in unmasking underlying differences between normal and pathological neural circuits.…”