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Inhibition within the nucleus tractus solitarius (NTS) ameliorates environmental exploration deficits due to cerebellum lesions in an animal model for autism.

Abstract：

:Clinical observations suggest that abnormalities within the cerebellum and/or the cerebellum--cholinergic forebrain connections may be key to explain the severe behavioral deficits and increases in seizures seen in autism. In order to explore functional relationships between brain areas implicated in many of the core behavioral features of autism, experiments utilizing animal models for specific autism-like behaviors have increased in recent years. In the current study, we used a rodent model for the autism-like behavior of environment exploration deficits to examine the role of the cerebellum and its connectivity to the forebrain. In addition, due to the possible common neural pathways between seizures and autism-like behaviors, we explored the possibility for limiting autism-like behaviors via antiseizure brainstem and cerebellar circuitry. In two experiments, adult male rats showed a significant decrease in exploration behavior following developmental cerebellar suction lesions (experiment 1) or i.c.v. saporin injections specifically targeting Purkinje cells, but not after the addition of saporin-induced cholinergic forebrain lesions (experiment 2). In both experiments, the anticonvulsant treatment of inhibition of the medullary nucleus tractus solitarius (NTS) restored exploration behavior to control levels. These findings suggest that specific neuronal populations within the cerebellum are responsible for mediating exploration behavior, and these neuronal populations are similar to the circuitry involved in limbic motor seizures in that they are sensitive to brainstem inhibition. Furthermore, these results suggest this connection could be utilized in order to control behavioral deficits seen in autism with treatments, such as vagal nerve stimulation, which are effective against pharmaco-resistant seizures.

journal_name

Behav Brain Res

journal_title

Behavioural brain research

authors

Walker BR,Diefenbach KS,Parikh TN

doi

10.1016/j.bbr.2006.08.008

subject

Has Abstract

pub_date

2007-01-10 00:00:00

pages

109-20

issue

1

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(06)00453-0

journal_volume

176

pub_type

杂志文章

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