Stress related memories contribute to fear, anxiety, social dysfunction, and depression. The researchers realized that stress systems affect memory and memory determines how humans think, then interpret how they feel about what they think. In this study that examined contextual fear conditioning (CFC), the researchers shocked the mice which resulted in behavioral changes. The shock has to come at the right time.The researchers were interested in what happens to memories after they reach the hippocampus. Memory in the hippocampus is time sensitive. After some time, the memory becomes hippocampus independent. They had ideas about how memories travel form the hippocampus to the RSC but could not understand how this happened. For these experiments, the researchers used mice to further understand this area of study. Animals learn in fear controlled environments. In CFC, they learn that after a certain time, the shock will arrive. Thus, animals fear in anticipation before the event and during the event. Furthermore, animals also learn to fear the context.
The dorsal hippocampal (DH) projects directly only to RSC. Furthermore, they found that glutameric neurotransmission in DH and RSC is required for CFC. RSC activity is required to process recent and remote memories. This suggests that the DH-RSC projections transmit contextual information required for cortical memory processing from early stages. The researchers studied the underlying mechanisms of DH-RSC and determined how these mechanisms play a role in storage and retrieval of fear-inducing context memories. Furthermore, they also found that vGlut1 and vGlut2 are neurons in DH that regulate RSC networks. They found that vGlut1 plays a role in encoding and retrieving memory an vGlut2 maintain this effect.
The researchers used a dug called DREADD so they could determine the functional role of DH-RSC projections in CFC. DREADD are designer receptors. Using DREADD avoids using heat and allows it to stay for longer periods of time. They delivered CNO into the RSC, which bound do DREADD. CNO blocks presynaptic release from axon terminals that does not impact the spiking activity of the neurons. They found that the CNO injected mice froze less. This asserts that the DH-RSC pathways have a great impact on encoding contextual memory.
vGlut1 and vGlut2. vGlut1 and vGlut2 both have different functions and they both activate glutamergic receptors. They found that vGlut2 is positive for RSC projecting DH. vGlut1 bursts continuously while vGlut2 bursts in fragments. vGlut1 is involved in retrieving, receiving and silencing memory. The researchers observed that vGlut1 does not take part in memory formation or retrieval. Silencing vGlut2 is positive for DH-RSC projections during encoding that impairs CFC. They found no relationship between the results of male and female mice.
The researchers tested the way DH impacts RSC activity. They focued this experiment on the excitation of pyramidal neurons and feedforward inhibition. They found that on slices from vGlut1 mice, the vGlut1 axons give a larger EPSC and IPSC in neurons superficial layers of the brain. This experiment using vGlut2 axons resulted in higher EPSC in pyramidal neurons in superficial layers. This experiment showed the vGlut1 and vGlut2 excite pyramidal neurons in both superficial layers and local interneurons through feedforward inhibition.
Furthermore, the researchers found that silencing vGlut1 and vGlut2 DH-RSCc terminals impacts encoding, consolidation and retrieval of CFC. Inactivating vGlut2 showed that the projections of vGlut2 DH-RSC became impaired. Thus, it appears that vGlut2 is important for context memory consolidation. When the researchers silenced vGlut1 DH terminals in RSC induced impaired freezing. Furthermore, silencing vGlut2 DH terminals did not impact memory retrieval. These findings show the influence of vGlut1 DH-RSC projections to receive recent context memories and vGlut2 in consolidating these memories.
References:
Naoki Yamawaki, Kevin A. Corcoran, Anita L. Guedea,Gordon M.G. Shepherd and Jelena Radulovic. Differential Contributions of Glutamatergic Hippocampal→Retrosplenial Cortical Projections to the Formation and Persistence of Context Memories. Oxford, 2018; 1-9. DOI: 10.1093/cercor/bhy142
No comments:
Post a Comment