ABSTRACT
Stimulus-specific adaptation (SSA), defined as a decrease in responses to a common stimulus that only partially generalizes to other rare stimuli, is a widespread phenomenon in the brain that is believed to be related to novelty detection. Although cross-modal sensory processing is also a widespread phenomenon, the interaction between the two phenomena is not well understood. In this study, the thalamic reticular nucleus (TRN), which is regarded as a hub of the attentional system that contains multi-modal neurons, was investigated. The results showed that SSA existed in an interactive oddball stimulation, which mimics stimulation changes from one modality to another. In the bimodal integration, SSA to bimodal stimulation was stronger than to visual stimulation alone but similar to auditory stimulation alone, which indicated a limited integrative effect. Collectively, the present results provide evidence for independent cross-modal processing in bimodal TRN neurons.
Subject(s)
Animals , Rats , Acoustic Stimulation , Auditory Perception/physiology , Geniculate Bodies , Rats, Wistar , Thalamic Nuclei/physiologyABSTRACT
Objective: To explore the mechanism of acupuncture in regulating cognitive deficits in insomnia rats by observing the effect of acupuncture on microglia in thalamic reticular nucleus (TRN). Methods: Thirty rats were randomly divided into a control group, a model group and an acupuncture group, with 10 rats in each group. The insomnia model was established by intraperitoneal injection of para-chlorophenylalanine (PCPA) once a day for 2 d. Rats in the control group were intraperitoneally injected with the same amount of normal saline. Rats in the acupuncture group received acupuncture at Neiguan (PC 6) and Zusanli (ST 36) for 5 consecutive days. The CLOCKLAB 2 data acquisition system was used to dynamically observe the sleep of the rats throughout the experiment. The cognition of rats was evaluated by event-related potentials (ERPs). After intervention, brain tissue was extracted. Immunofluorescence was used to test the fluorescence expression in TRN region. The concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay. Results: After intraperitoneal injection of PCPA suspension, the spontaneous activity in light period of rats in the model group and acupuncture group increased significantly compared with the control group (both P<0.01). After acupuncture treatment, the rats in the acupuncture group had much less spontaneous activity during the light period than those in the model group (P<0.01), and the results indicated that acupuncture could effectively improve the sleep quality of insomnia rats. Compared with the control group, rats in the model group showed that the P3 latency, the average optical density of microglia, and the concentrations of IL-1β and TNF-α increased significantly (all P<0.05), and the P3 amplitude decreased significantly (P<0.01). Compared with the model group, rats in the acupuncture group presented that the P3 latency, the average optical density of microglia, and the concentrations of IL-1β and TNF-α were significantly decreased (all P<0.05), and the amplitude of P3 was significantly increased (P<0.05). Conclusion: Acupuncture possesses an ability to improve the cognitive state in insomnia rats. The mechanism may be related to inhibiting the microglial activation, diminishing the levels of pro-inflammatory mediators like IL-1β and TNF-α, and promoting the recovery of central nervous system function.
ABSTRACT
Assessing the cell-type expression pattern of a certain gene can be achieved by using cell-type-specific gene manipulation. Recently, cre-recombinase-dependent gene-silencing tool, pSico has become popular in neuroscientific research. However, pSico has a critical limitation that gene-silenced cell cannot be identified by fluorescence, due to an excision of the reporter gene for green fluorescence protein (GFP). To overcome this limitation, we newly developed pSico-Red, with mCherry gene as a reporter outside two loxP sites, so that red mCherry signal is detected in all transfected cells. When a cell expresses cre, GFP is excised and shRNA is enabled, resulting in disappearance of GFP. This feature of pSico-Red provides not only cell-type-specific gene-silencing but also identification of cre expressing cells. Using this system, we demonstrated for the first time the neuronal expression of the Bestrophin-1 (Best1) in thalamic reticular nucleus (TRN) and TRN-neuron-specific gene-silencing of Best1. We combined adeno-associated virus (AAV) carrying Best1-shRNA in pSico-Red vector and transgenic mouse expressing cre under the promoter of distal-less homeobox 5/6 (DLX5/6), a marker for inhibitory neurons. Firstly, we found that almost all of inhibitory neurons in TRN express Best1 by immunohistochemistry. Using pSico-Red virus, we found that 80% of infected TRN neurons were DLX5/6-cre positive but parvalbumin negative. Finally, we found that Best1 in DLX5/6-cre positive neurons were significantly reduced by Best1-shRNA. Our study demonstrates that TRN neurons strongly express Best1 and that pSico-Red is a valuable tool for cell-type-specific gene manipulation and identification of specific cell population.