Short-term memory (STM).Information can be stored with a short delay time. How distant and local neural connections interact to support STM encoding is still poorly understood. On February 13, the Lingang Laboratory of the Center for Excellence in Brain Science and Intelligent Technology, Chinese Academy of SciencesLi Chengyu's research teamA study titled "Prefrontal Projections Modulate Recurrent Circuitry in the Insular Cortex to Support Short-Term Memory" was published in Cell Reports**. They explored long-range projection from the medial prefrontal cortex (MPFC) to the anterior agranular insular cortex (AAIC) by performing an olfactory delayed response task with a head-fixed mouse. Through optogenetics and electrophysiology experiments, they revealed that two regions, MPFC and AAIC, play an important role in the behavior of encoding STM information.
Spike-correlogram analysis showed that there were strong localities and cross-regions between memory neurons encoding the same informationFunctional coupling (FC).。During the delay, optogenetic inhibition of MPFC-AAIC projections reduced behavioral performance, the proportion of memory neurons, and memory-specific FC within AAIC, while optogenetic activation enhanced all of these abilities. In addition, MPFC-AAIC projection also bidirectionally regulates the efficiency of STM information transmission and can be measured by the contribution of FC-paired spike discharges to the memory encoding ability of subsequent neurons. Thus, prefrontal projections modulate the functional connectivity and memory encoding capacity of insular neurons in support of STM.
The delay period activity of the MPFC and AAIC maintains the STM information in the DRT.
Their previous study identified the importance of MPFC-AAIC projection for behavior and function under STM in the olfactory delayed paired association (ODPA) task. This study demonstrates a close association between behavioral performance and AAIC transient STM-encoding neurons under bidirectional optogenetic manipulation of MPFC-AAIC projections. This study aims to ** two unanswered questions:(1) whether the importance of this ** can be extended to other STM paradigms, and (2) how long-range connectivity regulates neuronal processing in downstream regions to support STM.
Brain function relies on cyclic connectivity, and neurons encoding the same information are connected into specific cellular assemblies through the fire-together-wire-together principle. However, how FC associated with STM is controlled by remote cortical projection remains unclear.
Our research team used an automated training system to train mice with fixed heads on the olfactory delayed-response task (DRT). In each DRT trial (Figures 1A and 1F), mice make a decision of "GO" or "NOGO" based on the characteristics of the sample odor. Mice need to stop licking within a delay period of 4 or 10 sec; Otherwise, the trial will end without a reward. This task requires mice to maintain information about upcoming locomotion behaviors, and for this reason, it is referred to as a "motion-oriented" STM task.
Therefore, the researchers explored the role of MPFC and AAIC delay-period activity in STM tasks. In the first 5 days of DRT study, the inhibition of optogenetic activity by MPFC or AAIC in the delayed phase significantly reduced mouse behavioral performance. In the subsequent well-trained phase, only inhibition of delayed phase activity in MPFC, rather than AAIC, can reduce mouse behavior. In conclusion, delay-period activity in MPFCs and AAICs is critical to maintaining STM information in DRT, especially during the learning phase.
Using in vivo single-cell electrical signal recording techniques, combined with Population Cross-Temporal Decoding (CTD) analysis and principal component analysis, the researchers further found that AAIC and MPFC neurons employ transient and persistent patterns during delay to encode motion-directed STM information, which correlates with behavioral performance. In addition, the results of the analysis for FC showed that AAIC neurons that received FC from MPFC memory neurons were more likely to exhibit memory selectivity than FC neurons from MPFC non-memory neurons. A similar pattern has been observed in local FC pairs. Thus, FC analysis revealed preferential functional connections between memory neurons.
The MPFC-AAIC circuit supports the neural mechanisms of STM behavior.
Further, the researchers utilized circuit-specific optogenetic manipulation to examine its potential causal contribution to behavior. Activation of the MPFC-AAIC loop by optogenetics improved DRT performance during learning. Next, the researchers found that the encoding memory neurons, memory-specific FC, and information transfer efficiency varied uniformly under AAIC bidirectional regulation. Thus, long-range MPFC-AAIC projections are able to modulate STM behavior by providing information-related inputs and driving drives cyclic connections between neurons encoding the same information (Figure 2).
Summary
The study shows:MPFC projection regulates downstream AAIC's encoding capacity and local ligation to support short-term memory. Under the optogenetic manipulation of MPFC-AAIC projection, memory encoding ability, FC and memory information transfer efficiency can be bidirectionally regulated in a way consistent with behavioral performance(Figure 3).