Churchland lab

This is a guest blog written by Ashley Kyalwazi, a participant in the Undergraduate Research Program at Cold Spring Harbor Laboratory. I am the director of the program, as well as the PI on our NSF-Funded grant (along with my bioinformatics colleague Mike Schatz) to train undergraduates in Bioinformatics and Computational Neuroscience. These fields share many mathematical ideas, such as a need for dimensionality reduction and machine learning tools, but our program is highly unusual in bringing them together. Ms Kyalwazi, one of our students funded by the program, will be a junior this upcoming year at the University of Notre Dame. Her story is below:

As I embarked on my ten-week long summer research immersion experience here at Cold Spring Harbor Laboratory, I was excited. To me this was an opportunity to listen to a vast range of new ideas in major scientific disciplines, to analyze them, and then to begin forming my own. I would always carry a notepad and a pen with me around campus; I never knew what I would learn on any given day, from any given individual. All I knew, for sure, was that I would grow as a scientist and as a future physician.

Working in the systems neuroscience lab of Dr. Stephen Shea has been an incredible experience. I have had the opportunity to learn a vast new array of techniques from my mentors in the Shea lab, and to apply them as I worked on an independent project that uses a mouse model in order to gain a deeper understanding of the inhibitory network of parvalbumin neurons in the auditory cortex, and how this network regulates neural activity before, during, and after what I have come to refer to as “the maternal experience.”

The maternal experience describes any aspect of the mother-pup interaction that contributes to the context of the overall birthing process. This could range from mothers giving birth, to the act of retrieving distressed pups that find themselves isolated from the nest.  The former is an action that is characteristic to a single mother and her pups; however, the latter is one that could be translated and studied with a model incorporating virgin female mice (‘surrogates’). In my project, I was interested in understanding how maternal experience alters the neural circuitry of the surrogate’s brain, primarily focusing on a network of neurons in the cortex defined by the marker parvalbumin (PV+ cells). This network has been found to play a key role in regulating plasticity in the auditory cortex of female mice, following interaction with newborn pups (Shea et al 2016). So again I ask: what is the nature of nuture?

Last week, during journal club, my lab read a paper by Lior Cohen, Gideon Rothschild, and Adi Mizrahi titled “Multisensory Integration of Natural Odors and Sounds in the Auditory Cortex.” This paper found that neurons in A1 of mothers, and other virgin female mice, integrate pup odors and sounds, suggesting an experience-dependent model for cortical plasticity.

One of the findings that intrigued me the most as I was reading this paper, was the observation that washing the pups hindered a lactating mother’s ability to retrieve them, after they became isolated from the nest. While the authors’ emphasis on this observation was the fact that pup odor is a commanding feature of pup-retrieval behavior, I was interested in this for a slightly different reason.

To know that an act as simple as washing the pups could change the behavior of something as innate as a mother retrieving her own pups led me to wonder: is there an essential biological component of motherhood that is necessary for a pup’s development and overall survival¾ or should we, as scientists, begin to hone in on the commonalities that make up the maternal experience, and also enable virgin females to successfully retrieve isolated pups?

My experiments this summer utilized a combination of stereotaxic surgery (injections and craniotomies), fluorescence imaging, computer programming and image analysis in order to observe the sound-evoked spatiotemporal activity patterns in the A1 PV+ network of naïve female mice.

Blue LED light was directed through cranial windows over the left auditory cortex and recordings of eight pup calls were emitted at regular intervals for each of the 20 trials. Plotting the average intensities for the activated region of interest across the 20 trials yielded a visual representation of the GCaMP6m activation in the parvalbumin neuronal population (Table 1).

This widespread cortical GCaMP6m activation throughout the A1 PV+ neuronal network suggests that, when exposed to pup calls, female mice do not tend to differentiate among varying frequencies. Perhaps this could be due the dependency of all pups to receive this nurturing behavior, and for mothers and surrogates alike to provide it.

This suggested binary distinction of female mice¾ recognizing ‘call vs. no call,’ but not distinguishing between ‘call frequency A vs. call frequency B’¾ is one that will be further investigated in the Shea lab, as we look to hone in on the neural circuits that regulate long-term, experience-dependent plasticity in the auditory cortex.

I would like to thank my research advisor for the summer, Dr. Stephen Shea, and the directors of the Undergraduate Research Program, Dr. Anne Churchland and Kim Creteur, for providing me with this opportunity. I also thank my parents¾ Michael and Winnie Kyalwazi. Against all odds you continue to work hard and sacrifice so I have opportunities as life-changing as coming to CSHL to study neuroscience… a dream come true. Your love and support has been and will never cease to be the wind beneath my wings. It has definitely been a memorable summer for me here at Cold Spring Harbor Laboratory and I look forward to the future.