Author: Danial Arslan

Danial Arslan

Social interactions are often thought to be one of the most basic human needs that exists, alongside the need to find food to eat and water to drink. Some even postulate that our brains evolved, over the millennia, due to selection pressures placed because of the social environments our ancestors lived in. This came to be known as the social brain hypothesis.

As it turns out this instinctive need to form social bonds transcends the human species.

Studies have found genes which regulate social behaviours in distant organisms like the Drosophila melanogaster, Caenorhabditis elegans and Microtus ochrogaster. Thus, it can be inferred that even these species have their own systems of social hierarchies, societies and social bonds.

A variety of neuropsychiatric disorders such as schizophrenia and autism spectrum disorders are characterized by disruptions in these social behaviours and bonds. Hence, there has been a recent surge in the study of the neural circuitry involved in forming social bonds in order to better understand these diseases. Since social bonds aren’t only restricted to humans, we can study these disorders by studying neural pathways involved in forming bonds in other species first.

My lab has been studying prairie voles (Microtus ochrogaster) due to their surprisingly monogamous nature (as described in my previous blog post here). Based on previous work done, the lab is trying to ascertain whether oxytocin or specific brain waves, between the nucleus accumbens and the medial prefrontal cortex regions of the brain, might be responsible for the formation of these monogamous relationships.

The current data which led to this finding has been based on analysing brain waves, alongside affiliative behaviours seen, while voles were cohabitating. However, in order to find a stronger correlation between our independent variables (oxytocin concentration or the frequency of brain waves between the two brain regions) and what we wanted to measure experimentally (the strength of the partner bond formed) we needed to devise a more straightforward test and this is what I and one of the graduate students in my lab, sought out to do.

And so after weeks of testing different theories, we came up with a 2 way odour expoure test that we will now use moving forward. The basic principle would be to ‘entrap’ the scent of two female voles. We did this by collecting the bedding used by the voles while singly caged. (Side note: Since vole’s love making burrows paper bedding is placed in their cages to keep them busy). This paper bedding successfully captured their smells and was added to a petri dish with an exact number of perforations on the top and bottom of the dish’s cover. This would allow the scent to be carried as air passed in through one set of perforations and moved out of the other.

After entrapping the female scent, one female would be cohabitated with the male vole to establish the pair bond and then the male vole would be placed in a cage with 3 compartments as shown in the diagram below:

The ‘partner’ would be the female the male was housed with and the ‘stranger’ would be the female who was never housed with the male. The male would be placed in the center compartment and his movement to different sides would be tracked.

Then after the assay, the time spent in each compartment would be analysed, as well as the time spent by the vole sniffing and investigating each of the petri dishes, to ascertain whether the vole preferred the partner compartment and petri dish over the other one.

Meanwhile, any vocalizations made by the vole in these different sides would also be recorded to see if the vole’s vocalizations differed when it was in a side of the cage where it could smell its partner to when it was in the stranger side.

A general outline of the entire procedure can be seen with this schematic:

And so, we came up with an odour exposure test which would be done by seeing which odour the vole would investigate more. The basic assumption was that the vole would deduce that the smell of the female vole would indicate her presence and so would call out to her. We tweaked around the time we cohabitated the voles for as well as the time of the partner preference test itself to see under what conditions we could obtain the best data and that would be used moving onwards.

So, in conclusion, our odour exposure test would look at how the male vole reacts and subsequently behaves to the presence of olfactory cues which give it the impression that it is close to its partner. Preference would be seen by looking at time spent in a particular side of the cage, time spent sniffing the petri dish and auditory calls made out when in a particular side. This data could then be used to see if the behaviours do in fact differ when the vole detects the partner scent or the stranger scent. If a significant difference is seen, then in the future a neurologger device could be inserted into the brain regions of interest to see the exact brain waves and levels of oxytocin present during these behaviours and hence this devised test could act as a standardized assay for future experiments in the field.

 

 

 

 

 

Danial Arslan – 11/07/17

RESEARCH UPDATE: I am currently learning about the current and past research being conducted in my lab and in other similar labs at Emory by attending talks held on campus as well as through weekly lab meetings where graduate students in the lab share articles they find interesting and discuss their recent findings. I am also going through the long, arduous process of gaining clearance at Yerkes to work on prairie voles, which includes learning how to operate on them in the most humane way while following aseptic techniques. However, to completely understand the complexity and significance of the research being pursued in the lab, my graduate mentor assigns a review paper to me on a weekly basis to bolster my basic understanding of Neuroscience. We then get together and discuss the paper after the weekly lab meeting. This week I read about the Nucleus Accumbens and the following blog is a brief introduction into the role and significance of this portion of the brain. To view my previous blog to read more about my research and goals click here.

To access the paper, I was assigned to read and from which the information below is taken, click here.

---

Since the discovery of the nucleus accumbens (NAc) in 1975, there has been extensive research on this compartment of the brain, especially in terms of the role this portion plays in providing motivation behind actions and ascribing ‘rewards’ to certain behaviours, such as after consuming drugs or food or after indulging in sexual acts. (Mogenson et al., 1993) As a result, this portion of the brain is colloquially referred to as the ‘pleasure center’ of the brain.

However, recently there has been a shift in the understanding of the role of the NAc in the brain, and with it there has been a shift in the research being done on this sector. This is what my assignment for this week was. To understand how the NAc worked and what had brought about the changes in its’ understanding.

The brain is divided into 3 portions. The cerebrum, which is the largest part of the brain, is responsible for controlling all voluntary actions, and is broken down into a series of lobes. Each lobe has a different brain function. (Picture adopted from Wikipedia).

The nucleus accumbens is extremely interconnected with the limbic system of the brain. behavior. It is proposed that the NAc receives mnemonic and emotional cues from nodes in the frontal and temporal lobes of the brain and relays the nervous impulses it receives to particular motor neurons to stimulate a set of responses. Since the NAc can prioritize the sequence of responses, therefore, it can influence the type and intensity of behaviour an organism expresses to a certain cue.

The limbic system of the brain. The parts of this system play a role in motivation, emotion, learning, and memory. (Picture adopted from Pearson.com)

The NAc can be broken down into two components based on its connectivity to other regions, namely the inner ‘shell’ and the outer ‘core.’ Impulses from various regions of the limbic region enter the NAc in particular sub regions leading scientists to speculate that the two portions play distinct roles. Within each region, there is an assemblage of cellular clusters, each of which receives impulses related to a particular type of input signal.

The impulses received by the NAc involve the excitatory neurotransmitter dopamine whereas the impulses which subsequently leave the NAc make use of the gamma-aminobutyric acid (GABA) neurotransmitter. By using this inhibitory GABA neurotransmitter, the cells in the NAc cannot stimulate the same motor neurons for prolonged periods of time (Pennartz et al. 1994, Uchimura et al. 1989). This means motivationally developed patterns of behaviour could not be formed by the activation of the neurons leaving the NAc and therefore changes in behavioural patterns must be formed due to changes in the excitation of the NAc by the incoming neural impulses transmitted from the temporal and frontal lobes through the glutamine neurotransmitter.

Therefore, it can be argued that the NAc is analogous to a messenger which passes information from the receiving end to the outgoing ‘motor’ end and that which outgoing pathway it conveys the message to or how many times it conveys the message is based on the suggestions or commands from the cortical and limbic regions of the brain rather than it being based on the judgement and determination of the NAc itself. One could say that the NAc acts like a ‘servant to many systems’ rather than acting like a decision-making center where it would ascribe responses on its own.

Figure adopted from the review paper.

Research findings also show that the reward-related actions which have been previously attributed to the NAc do not appear to in fact require the NAc at all. Reynolds & Berridge (1998), for example, showed that inactivating the NAc did not reduce food consumption by rats, but instead seemed to increase their appetite signifying that they were finding food consumption to be more rewarding when the neural activity of the NAc was suppressed.  Moreover, Berridge KC (2007) found that hedonic reactions exhibited after consuming food seemed to be independent of whether the NAc was suppressed or not. In conclusion, the pattern of actions done by individuals, related to gaining a ‘reward’ seems to be independent of the functioning of the NAc.

Therefore, the persistence to show that the neural accumbens as the ‘pleasure and reward system’ of the brain, might actually be a gross simplification and exaggeration of what the function and role of the neural accumbens in our brain really is. As a result, this particular portion of the brain continues to garner vast interest within the Neurobiology community, even 40 years after its discovery.

REFERENCES:

• Berridge KC. 2007. The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology 191(3):391–431
• Berridge KC, Robinson TE. 1998. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res. Rev. 28(3):309–69
• Pennartz CMA, Groenewegen HJ, Lopes Da Silva FH. 1994. The nucleus accumbens as a complex of functionally distinct neuronal ensembles: an integration of behavioural, electrophysiological and anatomical data. Prog. Neurobiol. 42(6):719–61
• Uchimura N, Cherubini E, North RA. 1989. Inward rectification in rat nucleus accumbens neurons. J. Neurophysiol. 62(6):1280–86
• Mogenson GJ, Brudzynski SM, Wu M, Yang CR, Yim CY. 1993. From motivation to action: a review of dopaminergic regulation of limbic→nucleus accumbens→ventral pallidum→pedunculopontine nucleus circuitries involved with limbic-motor integration. In Limbic-Motor Circuits and Neuropsychiatry, ed. PW Kalivas, CD Barnes, pp. 193–263. Boca Raton, FL: CRC Press
• Floresco, S.B., 2015. The nucleus accumbens: an interface between cognition, emotion, and action. Annual review of psychology, 66, pp.25-52.

---

A 2 minute recap on the  nucleus accumbens and what was discussed in this blog.

Danial Arslan – 10/6/2017

About Myself: 

My name is Danial Arslan and I am a sophomore at Emory University who is planning to pursue a (BS) degree in Biophysics and a (BS/MS) degree in Pure Mathematics. I am pre-med and am planning to later pursue the MD degree.

Introduction:

I will be working in Robert Liu’s lab at the Rollins Research Center.

Robert Liu runs a Computational Neuroethology lab which delves into the neural processes which are responsible for how an organism behaves. This includes studying how new neural connections form during social cues which can then later transform into behaviours for specific cues in organisms.

The lab also notes how neural plasticity can be regulated through manipulating neural mechanisms present in the ‘reward system’ of the brain. They are currently investigating specific topics within this broad research question. This includes understanding how female mice develop the ability to recognize their pups, through their offspring’s ultrasonic vocalizations. Moreover, the lab is also interested in exploring the social behaviours exhibited by prairie voles.

The lab is currently starting a new study into the electrophysiological mechanisms of social bonding in prairie voles, which is what I will be working on.

Overview of what the lab is working on now:

Adopted from the following paper:  Amadei, Elizabeth A., et al. “Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles.” Nature (2017).  This paper can be accessed by clicking here.

 

“The vole is closely related to the lemming and resembles a hamster.”¹

        Image adopted from: (Joel Sartore / National Geographic Creative)

The formation of monogamous relationships is not only complex but rare, with only 5% of current mammalian species actually demonstrating such ‘pair bonds’. These bonds are created when organisms undergo a series of biochemical and neurological changes which cause them to perceive their partners as ‘rewarding.’ However, there is still speculation as to how these neural mechanisms are formed during social interactions with partners.

In this paper, it is hypothesized that this rewarding mechanism is created through an increase in corticostriatal activity between the neural accumbens (NAcc) and the medial prefrontal cortex (mPFC). Corticostriatal circuitry plays a key role in creating motivation and forming goal oriented and reward seeking behaviours in organisms.² The authors of this paper therefore hypothesize that greater connectivity between the NAcc and the mPFC will result in an organism demonstrating more affiliative behaviours towards their mates.

The authors use a female prairie vole (Microtus ochrogaster) as their experimental model, to demonstrate social bonding. Prairie voles are extremely monogamous in nature and extremely affiliative, with males staying with their female mates and spending approximately half of their time in the nest with their pups.³

Individual variation in corticostriatal activity and the number of receptors for dopamine and oxytocin in the corticostriatal circuitry was shown to predict differences in affiliative behaviour. This was measured, in this experiment, by observing how quickly females would huddle with their partners after cohabitation.

Furthermore, activating this mPFC–NAcc circuit, during social scenarios with a specific mate, caused females to exhibit a preference for their mate. This showed that the corticostriatal activity was also responsible for escalating the affiliative behaviour. Therefore, this experiment showed how corticostriatal activity, during pair bond formation, could use the brain’s reward system to cause an increase in affiliative behaviour.

 

Where am I in the Research Process and Future Plans: 

 

A timeline outlining my goals for the coming year, in my research space.

I currently just joined the lab this week and have yet to go over previous articles the lab has published to get a sense of where they are now and where they are heading. I will be meeting up with my graduate fellow next week and will be working under him for the first semester. This will include going over various papers, related to this study, to become more knowledgeable in the field. Moreover, I will be working under his project in order to learn basic lab procedures, tests and techniques.

By January, I will be starting my own independent study, within this main research goal, with the hopes that by March I have at least some preliminary data which I can include in my scientific poster.

 

References:

1. Tucker, Abigail. “What Can Rodents Tell Us About Why Humans Love?” Smithsonian.com. Smithsonian Institution, 01 Feb. 2014. Web.
2. Haber, Suzanne N. “Corticostriatal Circuitry.” Dialogues in Clinical Neuroscience 18.1 (2016): 7–21. Print.
3. McGraw, Lisa A., and Larry J. Young. “The Prairie Vole: An Emerging Model Organism for Understanding the Social Brain.” Trends in neurosciences 33.2 (2010): 103. PMC.
4. Amadei, Elizabeth A., et al. “Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles.” Nature (2017).