Neuroscience
-
Hindlimb unloading (HU) in rats induces cardiovascular deconditioning (CVD) analogous to that observed in individuals exposed to microgravity or bed rest. Among other physiological changes, HU rats exhibit autonomic imbalance and altered baroreflex function. Lack of change in visceral afferent activity that projects to the brainstem in HU rats suggests that neuronal plasticity within central nuclei processing cardiovascular afferents may be responsible for these changes in CVD and HU. ⋯ These data demonstrate that HU increases presynaptic release and TS-EPSC amplitude, which includes a NMDA receptor component. Furthermore, the decreased excitability and hyperpolarized membrane after HU are associated with enhanced GABAergic modulation. This functional neuroplasticity in the nTS may underly the CVD induced by HU.
-
Changes in perineuronal nets (PNNs) after hearing loss were described in previous studies. The present study aimed to examine how single-sided deafness (SSD) affects the expression of excitatory and inhibitory synaptic transporters and PNNs in the primary auditory cortex (A1). Sprague-Dawley rats (8-week-old females, n = 30) were divided into three groups: (1) the SSD 2-week group (n = 10), (2) the SSD 4-week group (n = 10), and (3) the 4-week control group (n = 10). ⋯ The SSD groups had elevated expression levels of metalloproteinase (MMP) 9 on the contralateral side. The presynaptic glutamatergic and GABAergic transporters were increased in the A1 on the ipsilateral side after induction of SSD. Changes in the cortical auditory nervous system accompanied changes in the PNNs and their degradation enzymes MMP9 and MMP14.
-
K369I tau mice demonstrate a shift towards striatal neuron burst firing and goal-directed behaviour.
Pathological forms of the microtubule-associated protein tau are involved in a large group of neurodegenerative diseases named tauopathies, including frontotemporal lobar degeneration (FTLD-tau). K369I mutant tau transgenic mice (K3 mice) recapitulate neural and behavioural symptoms of FTLD, including tau aggregates in the cortex, alterations to nigrostriatum, memory deficits and parkinsonism. The aim of this study was to further characterise the K3 mouse model by examining functional alterations to the striatum. ⋯ The observed pattern of behaviour in K3 mice is suggestive of deficits in dorsal lateral striatal function and this was supported by our electrophysiological findings. Thus, both the electrophysiological and behavioural alterations indicate that K3 mice have early deficits in striatal function. This finding adds to the growing literature which indicate that the striatum is impacted in tau-related neuropathies such as FTLD, and further suggests that the K3 model is a unique mouse model for investigating FTLD especially with striatal involvement.
-
The incidence of mild cognitive impairment in Parkinson's disease (PDMCI) is as high as 18-55%. However, the pathological mechanism of PDMCI is not yet clear. Our previous research showed that microvascular pathology and chronic cerebral hypoperfusion participated in the occurrence and development of PDMCI. ⋯ When Nogo-A expression was downregulated, the cognitive and microvascular impairments were alleviated, and the expression of sphingosine-1-phosphate receptor 2 (S1PR2) and the RhoA/ROCK signaling pathway were inhibited. These findings suggested that Nogo-A could bind to S1PR2, activate related signaling pathways, and lead to the inhibition of vascular remodeling in PDMCI mice. This study indicated that Nogo-A downregulation could mediate microvascular remodeling and provide further insights into the pathogenesis of PDMCI.
-
Alterations in the functional organization of motor cortex and interictal motor deficits are observed in people with epilepsy. While seizures in the rat lead to more cortical area devoted to simple cortical forelimb movement representations (motor maps) assessed using short-duration intracortical microstimulation (ICMS), the effect of seizures on complex movements derived with long-duration ICMS is unknown. Further, the relationship between motor map expression and motor impairment is not well understood. ⋯ Bicuculline also significantly expanded forelimb motor maps (108%) but without increasing representational overlap. Moreover, expanded map areas in bicuculline rats evoked qualitatively distinct forelimb movements to long-duration, but not short-duration (n = 5), ICMS that were truncated. Our evidence indicates that motor map expansion following repeated experimental seizures is associated with reduced segregation between cortical movement representations that is not entirely due to reduced cortical inhibition but may contribute to interictal motor deficits in some individuals with epilepsy.