Deep learning based wavefront sensor for complex wavefront detection in adaptive optical microscopes

The Shack-Hartmann wavefront sensor(SHWS)is an essential tool for wavefront sensing in adaptive optical microscopes.However,the distorted spots induced by the complex wavefront challenge its detection performance.Here,we propose a deep learning based wavefront detection method which combines point spread function image based Zernike coefficient estimation and wavefront stitching.Rather than using the centroid displacements of each micro-lens,this method first estimates the Zernike coefficients of local wavefront distribution over each micro-lens and then stitches the local wavefronts for reconstruction.The proposed method can offer low root mean square wavefront errors and high accuracy for complex wavefront detection,and has potential to be applied in adaptive optical microscopes.

A Critical Role for γCaMKII in Decoding NMDA Signaling to Regulate AMPA Receptors in Putative Inhibitory Interneurons

CaMKII is essential for long-term potentiation(LTP),a process in which synaptic strength is increased following the acquisition of information.Among the four CaMKII isoforms,γCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons(LTPE→I).However,the molecular mechanism underlying howγCaMKII mediates LTPE→I remains unclear.Here,we show thatγCaMKII is highly enriched in cultured hippocampal inhibitory interneurons and opts to be activated by higher stimulating frequencies in the 10–30 Hz range.Following stimulation,γCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95.Knocking downγCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors(AMPARs)in putative inhibitory interneurons,which are restored by overexpression ofγCaMKII but not its kinase-dead form.Taken together,these data suggest thatγCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.

Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice

Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival.The zona incerta(ZI)has been demonstrated to play important roles in fear learning and fear memory,as well as modulating auditory-induced innate defensive behavior.However,whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown.Here,we found that somatostatin(SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus.Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus.Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia.In addition,we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens(Re)mediated fear-like defensive behavior.Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus(SC)that projected to the Re-projecting SST-positive neurons in the rostral ZI(SC-ZIrSST-Re pathway).Together,our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.

A Deep Mesencephalic Nucleus Circuit Regulates Licking Behavior

Licking behavior is important for water intake.The deep mesencephalic nucleus(DpMe)has been implicated in instinctive behaviors.However,whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown.Here,we found that the activity of the DpMe decreased during water intake.Inhibition of vesicular glutamate transporter 2-positive(VGLUT2+)neurons in the DpMe resulted in increased water intake.Somatostatin-expressing(SST+),but not protein kinase C-expressing(PKC-8+),GABAergic neurons in the central amygdala(CeA)preferentially innervated DpMe VGLUT2+neurons.The SST+neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior.Activation of these CeA SST+GABAergic neurons,but not PKC-8+GABAergic neurons,projecting to the DpMe was sufficient to induce licking behavior and promote water intake.These findings redefine the roles of the DpMe and reveal a novel CeAssT_DpMevcLUT?cireuit that regulaes icking behavior and promotes water intake.

Induction of Anxiety-Like Phenotypes by Knockdown of Cannabinoid Type-1 Receptors in the Amygdala of Marmosets

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases.Here,we investigated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.