Binocular visual experience drives the maturation of response variability and reliability in the visual cortex.

A fundamental challenge of neuroscience is to understand how a single neuron responds to multiple synaptic inputs effectively and reliably. In primary visual cortex, repeated stimuli to one eye elicit neuronal responses of inherent variability and reliability. However, it remains unclear how this monocular variability and reliability contribute to the establishment of effective and reliable binocular responses and what drives this development. In this study, using in vivo multichannel extracellular recordings, we demonstrate binocular responses in adult mouse visual cortex exhibit low variability and high reliability. This response characteristic is immature during the critical period of binocular vision development. In amblyopic mice, the maturation of binocular variability and reliability is disrupted, and this defect can be partially rescued by enhancing cortical plasticity via dark exposure. In conclusion, the development of cortical response variability and reliability depends on the normal binocular visual experience, which is further regulated by cortical plasticity.

Closing the Critical Period Is Required for the Maturation of Binocular Integration in Mouse Primary Visual Cortex.

Binocular matching of orientation preference between the two eyes is a common form of binocular integration that is regarded as the basis for stereopsis. How critical period plasticity enables binocular matching under the guidance of normal visual experience has not been fully demonstrated. To investigate how critical period closure affects the binocular matching, a critical period prolonged mouse model was constructed through the administration of bumetanide, an NKCC1 transporter antagonist. Using acute in vivo extracellular recording and molecular assay, we revealed that binocular matching was transiently disrupted due to heightened plasticity after the normal critical period, together with an increase in the density of spines and synapses, and the upregulation of GluA1 expression. Diazepam (DZ)/[(R, S)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP)] could reclose the extended critical period, and rescue the deficits in binocular matching. Furthermore, the extended critical period, alone, with normal visual experience is sufficient for the completion of binocular matching in amblyopic mice. Similarly, prolonging the critical period into adulthood by knocking out Nogo-66 receptor can prevent the normal maturation of binocular matching and depth perception. These results suggest that maintaining an optimal plasticity level during adolescence is most beneficial for the systemic maturation. Extending the critical period provides new clues for the maturation of binocular vision and may have critical implications for the treatment of amblyopia.

D1-like dopamine receptor dysfunction in the lateral habenula nucleus increased anxiety-like behavior in rat.

Lateral habenula (LHb) is important for emotional processing. It is a link node between forebrain and midbrain. LHb is reciprocally connected with ventral tegmental area, acting as a regulatory center for the dopaminergic system. However, the role of dopamine receptors in the LHb in emotional processing is less clear. In the present study, the expression of dopamine D1 and D2 receptors in LHb was testified by western blot. In addition, D1- or D2-like receptor agonist or antagonist was bilaterally administered into the LHb, anxiety-like and depressive-like behaviors were tested 15min later in rats. In addition, the effects of LHb dopamine receptor activation and inactivation on aversive learning and memory were assessed. Our results showed that: (1) activation and inhibition of D1R but not D2R in LHb increased anxiety-like behavior but decreased depressive-like behavior in rats. (2) D1R activation and inactivation in LHb impaired aversive memory acquisition but not consolidation in rats, D1R agonist also impaired aversive memory retrieval in rats. These results might provide new clues about how LHb was involved in emotional processing.

Dopamine D1-like receptor in lateral habenula nucleus affects contextual fear memory and long-term potentiation in hippocampal CA1 in rats.

The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats. We found that both D1R agonist and antagonist impaired the acquisition of contextual fear memory in rats. D1R agonist or antagonist also impaired long term potentiation (LTP) in hippocampal CA3-CA1 synapses in freely moving rats and attenuated learning induced phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at Ser831 and Ser845 in hippocampus. Taken together, our results suggested that dysfunction of D1R in LHb affected the function of hippocampus.