Tag: Santiago Jaramillo

Investigation of Training Methods Used for Mice to Perform Auditory Discrimination Tasks

Presenter: Sean Kyne – Biology

Faculty Mentor(s): Santiago Jaramillo

Session: (In-Person) Oral Panel—Stimuli and Response

The auditory system has a tremendous capacity to interpret all the surrounding sounds in the environment and help make sense of the world around us. To understand how our brains interpret and process complex sounds, we need a new method for studying auditory cognition. Researchers have created head-fixed rigs where mice run on a wheel while their head remains stationary and perform auditory discrimination tasks. This setting will allow us to study how the auditory system discriminates complex sounds using electrophysiological techniques that would be more challenging to apply in a freely-moving setting. Previous work in the lab suggests that it is more challenging to train mice in a head-fixed setting than in the more well-known freely moving setting. To improve our understanding of how to train head-fixed mice, they were trained to discriminate sounds of varying complexity. In each project, a new training protocol was implemented to increase our understanding of the best methods for training mice. The training protocols had varying success in teaching the task which provided helpful insights into teaching head-fixed mice auditory discrimination tasks.

Taking what was learned will allow us to teach mice more efficiently on future tasks using more complex sounds. Studying the methodology of how to train mice will allow for future experiments to use electrophysiological techniques to increase our understanding of the neural circuits used in auditory cognition.

Pupillary Dilation Response to Changes in Sound Stimuli

Presenter: Temerity Bauer − Biology

Faculty Mentor(s): Santiago Jaramillo

(In-Person) Oral Panel—Stimuli and Response, Poster Presentation

To understand the world around us, the auditory system of our brains discriminates between different sounds to interpret our surroundings. Normally, simple sounds (like pure tones) are used to study the neural mechanisms for processing sounds by training animals. Training animals to discriminate between sounds is an arduous endeavor. Further, using simple sounds limits our understanding of how the brain interprets sounds of the complexity that is experienced every day. To address these problems, we developed a methodology to study sound discrimination in naive mice without training the animals by using pupillometry.

Changes in pupil size is one of the many responses to stimuli an animal can have. A study performed by Montes-Lourido et al. found pupil diameter changes correlate with an increase in motivation, effort and arousal in the brain in subjects (Montes-Lourido et al., 2021). Previous studies found changes in pupil sizes to sounds like pure tones and animal calls (Montes-Lourido et al., 2021). We hypothesized pupil responses would occur when the animal is presented with complex sounds that are found in nature. To study natural complex sounds, we first had to establish if pupillary dilation responses occurred to changes in simpler sounds like chords. We found that the pupils exhibited a pupillary dilation response to changes in frequency. Through this project, we determined pupillary dilation responses can be used as a method to study frequency discrimination in mice.

Effect of Reward Size on the Activity of Auditory Cortical Neurons

Presenter(s): Jardon Weems − Biology

Faculty Mentor(s): Santiago Jaramillo

Poster 3

Research Area: Neuroscience

Funding: Peter O’Day Fellowship in Biological Sciences

The neural pathways that allow an animal to select the actions it should take in response to a sound in order to get a reward are not well understood. Recent work in our lab indicates that neurons in the region of the striatum that receive inputs from the auditory cortex fire differently in response to a sound when the sound is paired with a large reward in contrast to a small reward. These data suggest that the auditory striatum may integrate information about sound and reward size in a way that could support sound-action association learning. The primary aim of this study was to determine if reward related modulation observed in the striatal neurons is already present in the inputs arriving from the auditory cortex. To investigate whether auditory cortex integrates information about reward size during decision-making, we examined the activity of auditory cortical neurons in six male wild type C57BL/6J mice. Via chronically implanted electrodes, the mice performed an auditory reward- change task in which the same sound and same action was paired with different amounts of reward. We found that 7.5% of sound responsive auditory cortical neurons were modulated by the amount of reward during the decision-making task. In addition, we found a number of neurons in the auditory cortex that responded to movement, 21.8% of which were modulated by reward size. Our previous research found that 13.9% of sound responsive neurons in the auditory striatum and 25.7% of movement responsive neurons in the auditory striatum were modulated by reward size. Together, our results suggest that auditory cortex contributes to the integration of information about reward size and auditory stimuli during decision-making, but to a lesser extent than the auditory striatum.

Neuronal projections to the auditory striatum

Presenter(s): Cora Pyles

Faculty Mentor(s): Santiago Jaramillo & Nick Ponvert

Poster 57

Session: Sciences

The striatum, a brain area involved in decision making and learning, receives information from both the thalamus and the cortex. However, the precise cortical layers and thalamic nuclei that send auditory information to the striatum are unclear. To address this question, a retrograde viral approach was used in mice to label cells that project to the striatum, allowing quantification of striatal-projecting cells across thalamic nuclei and cortical layers. The study found that the projections from the thalamus come from non-lemniscal nuclei and projections from the auditory cortex come from layers 5 and 6. These results suggest that thalamostriatal neurons are located in nuclei that do not primarily project to the primary auditory cortex. Additionally, the results indicate that the striatum receives auditory information from multiple cortical layers, and each of these neuronal populations may convey different features about sounds to striatal cells. Understanding where striatal-projecting cells are located will allow for targeted extracellular recordings to characterize their neural responses evoked by different frequencies and amplitude modulations rates of sound.

The Role of the Auditory Cortex in Speech Sound Discrimination in Mice

Presenter(s): Erin Petruccione

Co Presenter(s): Temerity Bauer

Faculty Mentor(s): Santiago Jaramillo

Poster 49

 Session: Sciences

The ability to communicate in languages besides our native tongue is an important skill in a globalized world. In order to learn a new language, a person must learn new ways of categorizing speech sounds. While several strategies have been developed for second-language learning, the neural basis of how we learn a new language are largely unknown. To investigate the neural mechanisms responsible for learning sounds from a new language, we taught mice to discriminate between different sets of speech sounds. The anatomy and physiology of the auditory system of the mouse is such that principles learned in this animal model may provide important hypotheses for how learning occurs in humans. Mice were successfully able to categorize speech sounds according to spectral features (which differentiate the sound /ba/ from /da/) or temporal features (which differentiate /ba/ from /pa/). In the second part of the study, we used optogenetics to test whether mice were able to discriminate among speech sounds when their auditory cortex is inhibited. We accomplished this by expressing a light- sensitive protein in the neurons of the auditory cortex so they could be inactivated with green light. Preliminary data suggests a decrease in performance during optogenetic inactivation, indicating that categorization of some speech sounds in mice depends on the activity of the auditory cortex. A full characterization of how performance is affected during auditory cortex inactivation is underway. Identifying the neural mechanisms of speech sound categorization will inform better approaches for effectively and efficiently learning a foreign language.

The Role of Cortical Inhibitory Interneurons in Auditory Signal Detection

Presenter(s): Nadav Menashe

Faculty Mentor(s): Santiago Jaramillo

Poster 20

Session: Sciences

For years, researchers have been trying to uncover how different auditory areas in the brain allow us to segregate signals from a noise. The goal of this study was to use a mouse model to understand how two types of cortical inhibitory interneurons found in the auditory cortex, known as somatostatin-expressing (SOM) and parvalbumin-expressing (PV) interneurons, contribute to our perception of sound masked by noise. We hypothesized that suppressing the activity of auditory cortical SOM interneurons would decrease a mouse’s ability to detect a tone masked by noise when the background noise was composed of broadband signals. We expected a similar decrease when PV interneurons were suppressed when the background noise was composed of narrowband signals. To test these hypotheses, we taught transgenic SOM-ArchT and PV-ArchT mice how to perform a behavioral task where they had to determine if a pure tone was present in background noise. We then implanted optical fibers over their auditory cortex and they performed the same task while having their respective interneurons suppressed through an interaction between the light-sensitive ArchT protein and green light. We found that suppressing SOM interneurons decreased the percentage of trials in which the mice were able to detect a tone in all bandwidths of background noise, while suppressing PV interneurons did not affect performance, showing that they might not be important for mice to perform this task. These findings allow us to better understand the roles that different sources of inhibition play when detecting a sound masked by noise.

Neural and behavioral assays for studying predictive coding in the mouse brain

Presenter(s): Konrad Bailey

Faculty Mentor(s): Santiago Jaramillo

Poster 29

Session: Sciences

‘Controlled hallucination’ is a term that has been used to describe the process of interpreting sensory information according to the theory of predictive coding. This theory posits that the brain’s mechanisms for interpreting sensory information function by generating predictions about the external world and comparing these predictions to sensory signals. The objective of my study in the Jaramillo lab is to identify neuronal mechanisms for how the brain generates predictions about patterns of sounds. The resulting data will aid the process of testing the validity of the theory of predictive coding. In order to achieve an in-depth analysis of neuronal mechanisms for generating predictions the study requires a level of experimental access only available with animal test subjects. We use mice because of the range of available tools for monitoring and manipulating neural activity in this species. We trained a cohort of mice in a reward-driven behavioral task that required the animals to make predictions about incoming sounds. Our preliminary data suggests we were successful in training the mice to detect when a predicted pattern had been altered. Electrophysiological experiments will then be used to evaluate the neural basis of generating these predictions. Specifically, I will record the activity of auditory cortical neurons to evaluate how the sound patterns are represented when they’re expected vs. unexpected. The data we gather will help to either support or oppose the theory that we live in, as psychologist Chris Frith put it, ‘a fantasy that coincides with reality’.

Optical access to auditory cortex for in-vivo two-photon calcium imaging

Presenter(s): Raj Shah—Human Physiology

Faculty Mentor(s): Santiago Jaramillo, Beth McCarry

Session 5: The Wonders of the Brain

In vivo two-photon calcium imaging is a powerful tool that enables measuring activity of hundreds of individual neurons simultaneously . To understand how the brain makes predictions about sounds, we will use this imaging technique to measure how neurons from the auditory cortex of awake mice respond to expected and unexpected sounds . To image activity at the neuronal level, optical access is achieved via implantation of a cranial window . However, the auditory cortex is not easily accessible during surgery due its lateral location and large muscles and arteries around the ears . Here, we report an updated protocol for cranial window implantation over the auditory cortex for use in two-photon calcium imaging . With optical access to the auditory cortex, we are able to use in-vivo two-photon calcium imaging to evaluate sound-evoked responses of hundreds of auditory cortical neurons . These data will allow classifying and mapping the location of neurons that represent either predictions about a stimulus or errors in these predictions .

Characterization of sound-evoked responses of photo-identified auditory striatal neurons

Presenter(s): Matthew Nardoci—Biochemistry/Biology

Co-Presenter(s): Jewlyssa Pedregon

Faculty Mentor(s): Santiago Jaramillo

Session: Prerecorded Poster Presentation

The striatum plays a critical role in decision-making based on sensory input . Specifically, the posterior region of the striatum receives projections from auditory regions of both the cerebral cortex and the thalamus . This posterior region of the striatum contains several classes of neurons, but it is not known whether these distinct neuron classes respond uniquely to different sound stimuli . Specifically, the striatum contains two types of medium spiny neurons (MSNs) that form the direct and indirect pathways, suggesting that these MSNs play distinct roles . To test whether these two types of MSNs differ in their responses to sounds, we characterized evoked responses to basic acoustic stimuli such as pure tones and amplitude modulated white noise in naive mice . We discovered that the two populations of striatal neurons differ in the way they represent temporal modulations of sounds . This suggests that direct and indirect pathway neurons in the posterior striatum differently influence sound-driven decisions as they each process distinct sound features .