| Popis: |
Deep-brain stimulation (DBS) is increasingly being pursued as a treatment option for a range of neuropsychiatric disorders. When assessing its potential for the treatment of schizophrenia, related animal studies are often limited by the range of measurements that the equipment is capable of. In animals, the combination of DBS with various recording modalities such as local-field potential (LFP) recording has traditionally required complex and time-consuming laboratory setups. Furthermore, the elucidation of neural activity underpinning rodent behaviour has traditionally been hampered by the use of tethered systems and human involvement. Taken together, novel tools and techniques are required to drive forward DBS research in this area. In this study, two miniature wireless devices were developed for electrophysiological recording and stimulation in freely-moving rodents. The performance of one of these devices was verified in an open-field chamber, in which high-frequency (100Hz) st imulation was delivered bilaterally into the anterior thalamic nucleus at a range of current intensities (20(So(BA, 100(So(BA) and pulse-widths (25(So(Bs, 100(So(Bs, 200(So(Bs). LFP recordings were made bilaterally in the fronto-hippocampal brain regions. Not only was the recording/stimulation device able to successfully correlate electrophysiological recording and stimulation with animal behaviour (via video tracking), but a transient velocity increase of the animals was observed following stimulation at the higher current setting (100(So(BA). The effect of fimbria-fornix (FF) DBS (at 130Hz, 30(So(BA, 90(So(Bs) was then studied in a rodent disease model relevant to schizophrenia, using a spatial working memory paradigm inside a T-maze. Fronto-hippocampal LFP was recorded bilaterally, and was subsequently correlated to the rat's position using synchronised video-tracking. Notably, rat gamma-frequency LFP was found to be increased in all brain regions following an acute administration of the NMDA receptor antagonist phencyclidine (PCP; 3 mk.kg-p1s i.p.), which had persisted throughout the duration of the recording session. Furthermore, rat hippocampal theta-frequency activity was transiently elevated following a 30-second period of FF-DBS, which was carried out during the intra-trial delay period of the task. Finally, the use of FF-DBS throughout the task training sessions highlighted a (non-significant) tendency for rats to reach criterion performance faster than their sham-stimulated counterparts, highlighting the FF as a potential DBS target to consider with regards to disorders that affect learning and memory. The data presented in this study highlights a) the successful design and application of novel device technologies for enhancing the range of measurements in animal-related DBS studies, and b) the effects of FF-DBS in a rodent model relevant to schizophrenia, and its implications in the treatment of this disorder. |
