Molly Delaney, Class of 2022
Impairment of the medial prefrontal cortex, or mPFC, can lead to depression and many other psychiatric disorders. The mPFC has roles in effort-based decision making, judgement, memory and various emotional responses. Impaired dopamine levels can contribute to the development of psychiatric disorders, and the dopamine receptor cells in the mPFC can be investigated as indicators of such. The role of these dopamine-receptor cells is widely unknown and calls for further investigative research.
Ketamine is an antidepressant that is often used for individuals labeled as “treatment-resistant”, and is regulated by the mPFC (Hare 1). The primary neurons in the mPFC are pyramidal cells which are multipolar and have various roles. The underlying biomechanics of Ketamine and antidepressant responses is widely unknown. Researchers at the SSRN Electronic Journal, such as Brendan D. Hare and Ryota Shinohara, are currently investigating the roles that pyramidal cells may play in the mPFC in response to Ketamine administration. The two types of pyramidal neurons in the mPFC that are experimented with in this new study are the dopamine receptors Drd1 and Drd2 which are hypothesized to mediate antidepressant responses. The abundance of experiments completed in this recent study has lead these experimenters to conclude that Drd1 plays a crucial role in responses to Ketamine.
The study originally began as a question of what neuron subtypes in the mPFC played a role in depression, and this led to the analysis of pyramidal subtypes Drd1 and Drd2, which “have not been tested” before (Hare 2). The study begins with optogenetic stimulation of the ventral area of the mPFC. Optogenetic stimulation entails the manipulation of photostimulation of light-sensitive cells in the mPFC, which may lead to possible activation of Drd1 and Drd2 neurons. Through stereotaxic surgeries, some mice were injected with a Cre-dependent channelrhodopsin viral vector (AAV-Chr2). The mice injected expressed Drd1-Cre and Drd2-Cre, so both were injected with AAV-Chr2, or Cre for short, and then either mice was being used to study the two dopamine receptor cells. The mice underwent various photostimulations via optogenetics, and then their behavioral responses were tested. The mice underwent a forced swim test where “photostimulation of mPFC in Drd1-Cre mice produced an antidepressant response in the FST, measured by decreased time immobile” compared to the Wild Type mice who were not injected with the AAV-Chr2. Decreased time of the mice being immobile stipulates that the mice were not anxious. An anxious mouse would remain immobile as long as it can. The results of the forced swim test indicates a the Drd pyramidal cells’ role in antidepressant responses, specifically Ketamine. The mice also underwent another behavior experiment through the elevated plus maze, EPM. The mice spent a majority of the time in the open arms of the EPM which also indicates a reduction in anxiety as by being in the open arms of the maze, the mouse is exposed.
This current study is evolving and progressing, attempting to further complete the research about the biomechanics of ketamine and antidepressant responses. Understanding the biomechanisms will lead to future advances in the fight against mental illness. Understanding mental illness both biologically and socially will only lead to acceptance and community.
Works Cited
Hare, B. D., Liu, R. J., Shinohara, R., Pothula, S., Dileone, R. J., & Duman, R. S. (2018). Optogenetic Stimulation of Drd1 Expressing Neurons
Produces Rapid and Long-Lasting Antidepressant Effects. SSRN Electronic Journal. doi: 10.2139/ssrn.3155673
Ketamine is an antidepressant that is often used for individuals labeled as “treatment-resistant”, and is regulated by the mPFC (Hare 1). The primary neurons in the mPFC are pyramidal cells which are multipolar and have various roles. The underlying biomechanics of Ketamine and antidepressant responses is widely unknown. Researchers at the SSRN Electronic Journal, such as Brendan D. Hare and Ryota Shinohara, are currently investigating the roles that pyramidal cells may play in the mPFC in response to Ketamine administration. The two types of pyramidal neurons in the mPFC that are experimented with in this new study are the dopamine receptors Drd1 and Drd2 which are hypothesized to mediate antidepressant responses. The abundance of experiments completed in this recent study has lead these experimenters to conclude that Drd1 plays a crucial role in responses to Ketamine.
The study originally began as a question of what neuron subtypes in the mPFC played a role in depression, and this led to the analysis of pyramidal subtypes Drd1 and Drd2, which “have not been tested” before (Hare 2). The study begins with optogenetic stimulation of the ventral area of the mPFC. Optogenetic stimulation entails the manipulation of photostimulation of light-sensitive cells in the mPFC, which may lead to possible activation of Drd1 and Drd2 neurons. Through stereotaxic surgeries, some mice were injected with a Cre-dependent channelrhodopsin viral vector (AAV-Chr2). The mice injected expressed Drd1-Cre and Drd2-Cre, so both were injected with AAV-Chr2, or Cre for short, and then either mice was being used to study the two dopamine receptor cells. The mice underwent various photostimulations via optogenetics, and then their behavioral responses were tested. The mice underwent a forced swim test where “photostimulation of mPFC in Drd1-Cre mice produced an antidepressant response in the FST, measured by decreased time immobile” compared to the Wild Type mice who were not injected with the AAV-Chr2. Decreased time of the mice being immobile stipulates that the mice were not anxious. An anxious mouse would remain immobile as long as it can. The results of the forced swim test indicates a the Drd pyramidal cells’ role in antidepressant responses, specifically Ketamine. The mice also underwent another behavior experiment through the elevated plus maze, EPM. The mice spent a majority of the time in the open arms of the EPM which also indicates a reduction in anxiety as by being in the open arms of the maze, the mouse is exposed.
This current study is evolving and progressing, attempting to further complete the research about the biomechanics of ketamine and antidepressant responses. Understanding the biomechanisms will lead to future advances in the fight against mental illness. Understanding mental illness both biologically and socially will only lead to acceptance and community.
Works Cited
Hare, B. D., Liu, R. J., Shinohara, R., Pothula, S., Dileone, R. J., & Duman, R. S. (2018). Optogenetic Stimulation of Drd1 Expressing Neurons
Produces Rapid and Long-Lasting Antidepressant Effects. SSRN Electronic Journal. doi: 10.2139/ssrn.3155673
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