Biology subjects

Hwang, F.-J.

Publications and source records attributed to Hwang, F.-J..

3 recordsLinked to original sources

bioRxiv2022

Dichotomic Regulation of Striatal Plasticity by Dynorphin

Modulation of corticostriatal plasticity alters the information flow throughout basal ganglia circuits and represents a fundamental mechanism for motor learning, action selection, and reward. Synaptic plasticity in the striatal direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) are dichotomically regulated by two distinct networks of GPCR signaling cascades. While it is well-known that dopamine D2 and adenosine A2a receptors bidirectionally regulate iSPN plasticity, it remains unclear how D1 signaling modulation of synaptic plasticity is counteracted by a dSPN-specific Gi signaling. Here, we show that striatal dynorphin selectively suppresses long-term potentiation (LTP) through Kappa Opioid Receptor (KOR) in dSPNs. Both KOR antagonism and conditional deletion of dynorphin in dSPNs enhance LTP counterbalancing with different levels of D1 receptor activation. Behaviorally, mice lacking dynorphin specifically in dSPNs show normal motor behavior and reward-based learning, but enhanced flexibility during reversal learning. These findings support a model in which D1R and KOR signaling bidirectionally modulate synaptic plasticity in striatal direct pathways and behavior.

neuroscience↗

bioRxiv2021

Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons

Learning and consolidation of new motor skills require adaptations of neuronal activity and connectivity in the motor cortex and striatum, two key motor regions of the brain. Yet, how neurons undergo synaptic changes and become recruited during motor learning to form a memory engram remains an open question. Here, we train mice on a single-pellet reaching motor learning task and use a genetic approach to identify and manipulate behavior-relevant neurons selectively in the primary motor cortex (M1). We find that the degree of reactivation of M1 engram neurons correlates strongly with motor performance. We further demonstrate that learning-induced dendritic spine reorganization specifically occurs in these M1 engram neurons. In addition, we find that motor learning leads to an increase in the number and strength of outputs from M1 engram neurons onto striatal spiny projection neurons (SPNs) and that these synapses form local clusters along SPN dendrites. These results identify a highly specific synaptic plasticity during the formation of long-lasting motor memory traces in the corticostriatal circuit. HIGHLIGHTS- Motor performance is correlated with the reactivation of motor engram neurons - Motor learning increases spine density and new spine survival selectively on M1 engram neurons - Motor learning strengthens motor engram outputs to the striatum - M1 engram outputs converge onto clusters of dendritic spines on striatal spiny projection neurons

neuroscience↗

bioRxiv2021

A positively Tuned Voltage Indicator Reveals Electrical Correlates of Calcium Activity in the Brain

Neuronal spiking activity is routinely recorded using genetically encoded calcium indicators (GECIs), but calcium imaging is limited in temporal resolution and does not report subthreshold voltage changes. Genetically encoded voltage indicators (GEVIs) offer better temporal resolution and subthreshold sensitivity, but spike detection with fast GEVIs has required specialized imaging equipment. Here, we report the ASAP4 subfamily of genetically encoded voltage indicators (GEVIs) that brighten in response to membrane depolarization, inverting the fluorescence-voltage relationship of previous ASAP GEVIs. Two variants, ASAP4b and ASAP4e, feature 128% and 178% fluorescence increases over 100-mV of depolarization, respectively, facilitating spike detection in single trials in vivo with standard 1 and 2-photon imaging systems. Simultaneous voltage and calcium imaging confirms improved temporal resolution and spike discernment by ASAP4 GEVIs. Thus, positively tuned ASAP4 voltage indicators enable recording of neuronal spiking activity using similar equipment as calcium imaging, while providing higher temporal resolution. One Sentence SummaryUpward ASAPs increase detection capability of GEVIs in vivo.

neuroscience↗