Chen, H.-S. | Search bioRxiv

bioRxiv2022

A longitudinal CA2/3 to CA1 circuit for initiating context-dependent associative learning

Associating environmental context with emotional experience is a vital brain function that requires the activity in both dorsal and ventral hippocampus. While only ventral hippocampus connects with the amygdala, a hub for fear learning, it remains unclear how the two hippocampal areas interact during contextual fear conditioning (CFC). We found that projections from dorsal CA2/CA3 (dCA2/3) to the dorsal part of ventral CA1 (vCA1d) contributed significantly to CFC. Deep-brain Ca2+ imaging revealed a CFC-enhanced difference in neuronal activities evoked by conditioned vs. neutral environmental context in both dCA2/3 and vCA1d areas. Notably, contextual fear retrieval correlated with changes in conditioned context-evoked activity in vCA1d, but not in dCA2/3. Furthermore, slice recordings showed that CFC potentiated dCA2/3-to-vCA1d projection strength, in line with coordinated elevation of monosynaptic excitation and reduction of disynaptic inhibition mediated by somatostatin-expressing interneurons. Thus, vCA1d represents a critical site for initiating emotional association with contextual information from dCA2/3.

neuroscience↗

bioRxiv2021

An intein-split transactivator for intersectional neural imaging and optogenetic manipulation

The complexity of brain circuitry is manifested by numerous cell types based on genetic marker, location and neural connectivity. Cell-type specific recording and manipulation is essential to disentangle causal neural mechanisms in physiology and behavior; however, many current approaches are largely limited by number of intersectional features, incompatibility of common effectors and insufficient gene expression. To tackle these limitations, we devise an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in specific cell types defined by a combination of multiple features. We validate the specificity and sufficiency of IBIST to control common effectors including fluorophores, optogenetic opsins and Ca2+ indicators in various intersectional conditions in vivo. Using IBIST-based Ca2+ imaging, we show that the IBIST can intersect up to five features, and that hippocampal cells tune differently to distinct emotional valences depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and is compatible with common effectors to effectively control gene expression, monitor and manipulate neural activities.

neuroscience↗