Unilateral stimulation of the lateral division of the dorsal telencephalon induces synaptic plasticity in the bilateral medial division of zebrafish.

This study was aimed to evaluate the synaptic plasticity in projections from the dorsal lateral region (Dl) to the bilateral dorsal medial region (Dm) of the zebrafish telencephalon. The results showed that unilateral electrical stimulation of the Dl evokes a negative field potential (FP) in both the contralateral and ipsilateral side of the Dm. We tested synaptic plasticity, including high-frequency stimulation-induced LTP (HFS-LTP) and low-frequency stimulation-induced LTD (LFS-LTD). We demonstrated that HFS-induced bilateral LTP is NMDAR-dependent by the application of an NMDAR antagonist, DL-AP5 (30 µM, suprafused for 10 min), which blocked the HFS-induced LTP in both the contralateral and ipsilateral Dm. In addition, LTP was restored after DL-AP5 was washed out by continuous aCSF suprafusion. These results suggested that the potentiation is NMDAR-dependent. Either LFS (1 Hz for 20 min) or applying the mGluR agonist, DHPG (40 µM, suprafused for 10 min) successfully induced bilateral LTD for at least 1 h. Furthermore, both the contralateral fEPSP and LTP vanished after ablation of the anterior commissure. In conclusion, the results of the present study suggested that the projection between the Dl and contralateral Dm in the telencephalon of zebrafish is via the anterior commissure and possesses synaptic plasticity.

Fragile X Mental Retardation-1 Knockout Zebrafish Shows Precocious Development in Social Behavior.

Fragile X syndrome (FXS) is a generally hereditary form of human mental retardation that is caused by triplet repeat expansion (CGG) mutation in fragile X mental retardation 1 (fmr1) gene promoter and that results in the absence of the fragile X mental retardation protein (FMRP) expression. The common symptoms of FXS patients include learning disabilities, anxiety, autistic behaviors, as well as other behavioral abnormalities. Our previous results demonstrated the behavioral abnormalities in fmr1 knockout (KO) zebrafish such as fear memory impairment and autism-like behavior. Here, we studied the functional role of fmr1 gene on the development of social behavior by behavioral experiments, including shoaling behavior, shoaling preference, light/dark test, and novel tank task. Our results demonstrated that precocious development of shoaling behavior is found in fmr1 KO zebrafish without affecting the shoaling preference on conspecific zebrafish. The shoaling behavior appeared after 14 days postfertilization (dpf), and the level of shoaling elevated in fmr1 KO zebrafish. Furthermore, the fmr1 KO zebrafish at 28 dpf expressed higher anxiety level in novel tank task. These results suggest that the change of shoaling behavior in fmr1 KO zebrafish may result from hyperactivity and an increase of anxiety.

Stimulation of the lateral division of the dorsal telencephalon induces synaptic plasticity in the medial division of adult zebrafish.

In ray-finned fishes, the lateral (Dl) and medial (Dm) division of the dorsal telencephalon are important in learning and memory formation. Tract-tracing studies revealed that neural connections are formed between these regions via afferent Dl fibers projecting to the Dm. However, research analyzing Dl-Dm synaptic transmission is scant. We have used electrophysiological techniques to assess neurotransmission and synaptic plasticity in projections from the Dl to the Dm in zebrafish. We demonstrate that electrical stimulation of the Dl division evoked a negative field potential in the Dm division that could be inhibited by application of the AMPA/kainate receptor antagonist, CNQX (5µM). Pairs of stimuli, when delivered at brief inter-pulse intervals (IPI), elicited paired pulse facilitation (PPF). Long-term potentiation (LTP), induced through the application of three trains of high frequency stimulation (HFS; 100Hz for 1s), lasted for more than 1h and could be inhibited with DL-AP5 (40µM), an N-methyl-d-aspartate (NMDA) receptor antagonist. Our results suggest that the intratelencephalic connection between Dl and Dm may play an important role in the synaptic plasticity of the zebrafish brain. It also provides a new electrophysiological model for studying the neural mechanisms underlying learning and memory in zebrafish.

Effect of MK-801-induced impairment of inhibitory avoidance learning in zebrafish via inactivation of extracellular signal-regulated kinase (ERK) in telencephalon.

N-Methyl-D-aspartate (NMDA) receptors are implicated in a wide range of complex behavioral functions, including cognitive activity. Numerous studies have shown that using the repetitive administration of a noncompetitive NMDA receptor antagonist, MK-801, induces amnesia in rodents. In this study, the effect of a subchronic MK-801 treatment on the cognitive function of zebrafish was evaluated using a novel inhibitory avoidance task. First, we established a new system to investigate the inhibitory avoidance learning of zebrafish where they were trained to refrain from swimming from a shallow compartment to a deep compartment in order to avoid electric shock. Second, we found that blocking NMDA receptors by MK-801 could significantly attenuate the inhibitory avoidance behavior of the zebrafish and alter the telencephalic extracellular signal-regulated kinase (ERK) phosphorylation level 90 min after the inhibitory avoidance training. These results suggest that the formation of long-term emotional memory is possibly mediated by ERK activation in the telencephalon of zebrafish.

Resveratrol protects rats from Aß-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation.

Alzheimer disease (AD) is an age-dependent neurodegenerative disease characterized by the formation of ß-amyloid (Aß)-containing senile plaque. The disease could be induced by the administration of Aß peptide, which was also known to upregulate inducible nitric oxide synthase (iNOS) and stimulate neuronal apoptosis. The present study is aimed to elucidate the cellular effect of resveratrol, a natural phytoestrogen with neuroprotective activities, on Aß-induced hippocampal neuron loss and memory impairment. On adult Sprague-Dawley rats, we found the injection of Aß could result in a significant impairment in spatial memory, a marked increase in the cellular level of iNOS and lipid peroxidation, and an apparent decrease in the expression of heme oxygenase-1 (HO-1). By combining the treatment with Aß, resveratrol was able to confer a significant improvement in spatial memory, and protect animals from Aß-induced neurotoxicity. These neurological protection effects of resveratrol were associated with a reduction in the cellular levels of iNOS and lipid peroxidation and an increase in the production of HO-1. Moreover, the similar neurological and cellular response were also observed when Aß treatment was combined with the administration of a NOS inhibitor, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME). These findings strongly implicate that iNOS is involved in the Aß-induced lipid peroxidation and HO-1 downregulation, and resveratrol protects animals from Aß-induced neurotoxicity by suppressing iNOS production.