Molecular dissection of hippocampal inhibitory interneuron circuits
The purpose of this project is to use a molecular approach to determine the role of different types of cortical inhibitory interneurons in learning and memory. The cortical network contains a mixture of excitatory and inhibitory interneurons. A hallmark feature of interneurons is the high degree of diversity. To determine interneuron functions in a cell type specific manner, we will use the virus-mediated gene delivery technique to manipulate and record the activity, as well as identify molecularly defined interneuron subtypes. To target our analyses to specific cortical areas, we will perform stereotaxic surgery to deliver viral vectors to these brain structures in mice that express cre-recombinase in molecularly defined neuron types.
Preliminary results indicate that the role of modulatory systems on learning and memory may depend on their modulation of inhibitory cells (Society for neuroscience 2023 annual meeting, poster 110.07). We want to add Gad-Cre mice, which express the cre-recombinase in inhibitory cells in the brain, into this project. To perform control in vivo experiments, we will use wild-type mice. The aforementioned transgenic mice will be crossed with wild-type mice to produce heterogeneous offspring. Wild-type mice will used for both in vivo data acquisition and breeding purposes.
New mouse lines 2025: the animals will be subjected to the same experiments described in the original FOTS.
New lines will give us a molecular leverage to make a comprehensive analysis how emotion influences learning and memory.
Distress: moderate. Stereotaxic surgery under general anesthesia and local analgesics is associated with discomfort and pain. The expression of the exogenous genes in this project alone will not cause suffering of the animal because the product of these genes in the brain remains inactive without light.
We expect that this project to bring new perspectives in the mechanism of learning and memory, as well as how dysfunctions of cortical neural circuits contribute to brain diseases and disorders.
We will use transgenic mice that specifically express the cre-recombinase in molecularly defined neuron types. A detailed list of these mouse lines is given in the main body of the application.
We will implement the 3R with the follow approach.
First, we aim to use the results obtained from animal research to build models for simulating brain functions with the long-term goal to Replace animal research in in silico simulations.
Second, we will Reduce the number of animals by performing multiple and repeated measurements from each successful experiment, as well as by carefully designing of our research protocols to minimize the loss of animals.
Third, we support the Refinement of animal research by using anesthetic and analgesic agents to reduce the suffering, pain, and distress of animals.
Preliminary results indicate that the role of modulatory systems on learning and memory may depend on their modulation of inhibitory cells (Society for neuroscience 2023 annual meeting, poster 110.07). We want to add Gad-Cre mice, which express the cre-recombinase in inhibitory cells in the brain, into this project. To perform control in vivo experiments, we will use wild-type mice. The aforementioned transgenic mice will be crossed with wild-type mice to produce heterogeneous offspring. Wild-type mice will used for both in vivo data acquisition and breeding purposes.
New mouse lines 2025: the animals will be subjected to the same experiments described in the original FOTS.
New lines will give us a molecular leverage to make a comprehensive analysis how emotion influences learning and memory.
Distress: moderate. Stereotaxic surgery under general anesthesia and local analgesics is associated with discomfort and pain. The expression of the exogenous genes in this project alone will not cause suffering of the animal because the product of these genes in the brain remains inactive without light.
We expect that this project to bring new perspectives in the mechanism of learning and memory, as well as how dysfunctions of cortical neural circuits contribute to brain diseases and disorders.
We will use transgenic mice that specifically express the cre-recombinase in molecularly defined neuron types. A detailed list of these mouse lines is given in the main body of the application.
We will implement the 3R with the follow approach.
First, we aim to use the results obtained from animal research to build models for simulating brain functions with the long-term goal to Replace animal research in in silico simulations.
Second, we will Reduce the number of animals by performing multiple and repeated measurements from each successful experiment, as well as by carefully designing of our research protocols to minimize the loss of animals.
Third, we support the Refinement of animal research by using anesthetic and analgesic agents to reduce the suffering, pain, and distress of animals.