Shank-3-Deficient Rat Model

Attentional deficits in Shank-3 deficient rat model
Attention deficits are often associated with both PMS and ASD. Thus, we assessed performance in the attentionally demanding 5-choice serial reaction time (5-CSRT) task in which rats must respond quickly to briefly presented light cues (Fig. 1A). Both the Shank3 Het and KO rats learned the task and were able to reach baseline, similar to WT controls (criteria were accuracy rates higher than 80% for two consecutive days with omission rates lower than 20%). However, both the Shank3 Het and KO rats had lower accuracy and lower omission rates, when compared to WT rats, even upon extensive training. Moreover, after reaching baseline criterion Shank3-deficient rats did not maintain even this level
When PMS is diagnosed as ASD, behavioral and psychological treatments are considered the first line of the intervention strategy [45]. Pharmacological treatments of the core and often devastating deficits in ASD do not exist. Recently, the field has begun to translate basic neurobiological findings gleaned from mouse models into promising pharmacological treatments for a host of genetic disorders such as Fragile X syndrome, Tuberous sclerosis, Rett syndrome, and PMS [46-49]. Genetically modified rat models are especially valuable for behavioral and functional studies. They have several species-specific advantages over mouse models, including a more complex behavioral repertoire and larger brains that readily facilitate high-density electrophysiological recordings. Moreover, rats remain the primary choice of the pharmaceutical industry for studying the pharmacokinetic (PK) properties of novel drugs that may have therapeutic potential. Our results demonstrate that Shank3 deficiency in rat impairs its attention while performing visually attentive and demanding tasks. Deficits in such tasks may be a result of blunted synaptic plasticity, where brief events must be rapidly encoded and reliably stored by neural circuits to promote appropriate and timely behavior. Since pharmacological treatments for such fundamentally severe deficits in ASD do not exist, the results we found provides oxytocin as a potential therapeutics. Our results show for the first time, a beneficial effect of oxytocin on attention to brief stimuli. Attentional deficits are often co-morbid in attention-deficit disorder (ADHD) and ASD, [52] which is perhaps reflective of a shared etiology between the ASD and may explain why oxytocin improved both deficit types in Shank3 deficient rats. We