Week 5

Of the two papers this week, I enjoyed reading the 2008 Herry et. al paper by far. Having some knowledge of the concepts of extinction and conditioning and the fear circuit aided in my comprehension of the Herry paper, and overall I found it to be very clear and concise. I additionally appreciated how the experiments in the Herry paper clearly followed a logical procession. However, I struggled to understand the 2014 Courtin et. al paper and found it significantly more challenging than papers previously discussed in this class. As many of my peers have addressed, the concept of theta firing and phase resetting was extremely confusing. I had no prior knowledge of this subject, so I have some questions regarding this concept: what exactly is the significance of phase resetting and synchronized firing, and in what other processes is theta firing specifically involved? While I understand the authors likely assumed the readers would have background information regarding the paper’s more abstract topics, I would have appreciated if the authors had elaborated on and reminded its readers of the significance of each finding and its relevance to the original hypothesis. I also recognize that some additional research would help me better appreciate this paper, but after analyzing the research I am still feeling perplexed and overwhelmed by these concepts.

I found the clinical applications of these findings to be exciting because the fear circuit is so heavily involved in psychiatric disorders like PTSD and phobias. Exposure therapy is already one important therapeutic application involving extinction of a fear response that employs repeated exposure to diminish the original fear response. It would be interesting if therapies using optogenetics or electrophysiology could eventually target fear and extinction neurons specifically, either to suppress the exaggerated fear neurons’ response seen in psychiatric patients or enhance the extinction neurons’ activity.

Week 5

During my first co-op I worked as a behavioral therapist serving children with autism and other behavioral disorders. After that experience I have always had an interest in the neuronal processes and brain activity that occurs during events such as reinforcement, punishment and extinction. The 2008 paper was helpful in starting to answer some of the questions I had in regards to the neural networks responsible for these behaviors and occurrences. The Courtin et al. paper was interesting to me because during my second co-op my project involved optogenetic manipulation of parvalbumin interneurons in the visual cortex in mice. While reading relevant literature, I learned that these interneurons had differential and specific roles depending on their location in the cortex. Though interesting, I found the Courtin paper heavy in electrophysiology, which is not my strong suit, so my discussion focus is for the Herry paper.

Unfortunately, I had a difficult time comprehending many of this week’s figures and the discussion of the theta waves/theta resetting. I’ve come across this confusion before, but I still have yet to grasp the implications of the different waveforms on brain activity and neuronal function. I found the 2008 paper the easier of the two to read and get through. I had never taken the time to consider that extinction would be controlled by a distinct population of neurons whose activity opposed a population of fear neurons. I really liked how they addressed the question of whether the extinction and fear neurons could reverse roles – while it’s important to use controls and determine whether the populations were functionally distinct, it was phrased in a way which wouldn’t have immediately come to my mind. I found the flow of the paper as natural, the results of each experiment posed new questions that were addressed in the consequent experiments. This paper absolutely helped me begin to understand the neural mechanisms that are responsible, in part, for extinction.  

week 5

I’m glad I’m not the only one to say this, but like many others, I found the paper by Courtin et al (2013) extremely difficult to follow simply because they addressed various subtypes of neurons, their correlation with freezing, and various oscillation procedures that I am not familiar with. Even though I spent a lot of time trying to dissect and make sense of the paper, I still feel completely lost. Because of this limitation, I was not able to fully understand the depth of research or the take home message associated with it. Hopefully, after tomorrow’s discussion that won’t be the case.

Compared to the 2013 paper, Herry et al (2008) was much easier to follow as their approach was simplistic and I am familiar with the concepts of fear conditioning and extinction. Additionally, their experiments seemed to have a logical flow and seemed to build off each other, which makes it easier to understand. It was interesting to learn about the distinct types of neurons (fear and extinction neurons) and how they represent functionally different classes that have the ability to distinguish between the contexts the animal is in. I also found the concept of emotional perseveration to be quite cool – wish they had more to say about it. Having said that, I was not fully convinced with some of the conclusions made in the paper. For example, in the section titled “rapid reversal of activity during fear renewal’’, the authors found that - After successful recall of extinction memory (Fig. 4b), mice were transferred to the context in which they had been initially fear conditioned. Changing context resulted in a modest, but significant, increase in baseline freezing levels owing to contextual fear conditioning (Supplementary Fig. 3), and in a full renewal of the original cued fear memory. I was a little confused after reading this because isn’t fear extinction carried out in the same context as the one in which the animal was fear conditioned in? So why would they carry out extinction in a different context? Another point in the paper that left me puzzled was - Comparing the averaged time courses of CS-evoked activity of fear and extinction neurons during the acquisition of behavioural extinction indicated that significant behavioural changes occurred after the activity scores of the two populations of neurons crossed over. What do they mean by “crossed over”?

Week 5

Herry et al

I liked reading this study, found it interesting in how it is able to identify two neuron types in encoding fear and extinction. Also interesting to know how these neuron types relationship to other parts of the brain like the hippocampus and mPFC. I wonder though if they could have used more of a variety of fear conditioned stimulus like say an appearance of new object when shocked, it might be redundant but at least you could have more evidence to say it was fear encoding in general not just auditory fear encoding. Overall though again might not be necessary. I would also like to see the specific neurons ablated individually, to see the behavioral results, but since they overlap pretty close to each other it might be to difficult to do right now.

Courtien et al

This paper  I think might be written slightly better than the other paper. Because it focused on a lot of different neuro variables to try and explain extinction and fear learning, whereas the other paper I feel didn't do that as much. I also like that they were able to isolate specific neurons and test it behavioral outcomes which i think is important. If i were to say one thing that i might add is the same thing that I suggested under Herry et al which is to use another CS. I agree with the author that the results of this paper could have important application to disorders that might have a fear component to them.

Herry & Courtin

I got the overall point of the Herry et al. paper, the questions being asked, the methods by which the questions would be answered, and the overall conclusions. However, I couldn’t make sense of a bunch of the figures. Obviously, I knew that figures regarding neuronal activation and how it switches between the fear and extinction neuronal sets were being presented but I often couldn’t quite see how. Right off the bat, the raster plots and histograms through me off and it didn’t get any better from that point on as I couldn’t figure out what the z-score plots were showing. 

Although I had a hard time with the figures, I liked this paper mostly because I agreed with their thought progression. They start off showing the relation between BA neurons and fear and extinction then talk about how the two sets of neurons are different but share the same space and then move on to talk about the circuits these neurons are involved in and how they overlap or don’t overlap in terms of the mPFC and vHip, respectively. They then go on to show necessity of the BA neurons for behavioral changes through inactivation. Overall, I thought this was a well put together paper and I will likely appreciate it even more one I know what all the figures mean.

In terms of the Courtin et al. paper, all I got from it is that they are inhibiting certain neurons and this affect fear expression somehow. Outside of that, I don't know what is going on. I can’t really piece together the big picture of the paper as they just seem to jump right in to their data, or at least it feels that way to me. I definitely have a knowledge void in terms of the details of their experiments. I thought the figures would help, as they tend to do in papers that make sense but, well, they didn’t.