bioRxiv Science⌕ Search

Biology subjects

Drotos, A. C.

Publications and source records attributed to Drotos, A. C..

4 recordsLinked to original sources

Neurons in the inferior colliculus use multiplexing to encode features of frequency-modulated sweeps

Within the central auditory pathway, the inferior colliculus (IC) is a critical integration center for ascending sound information. While IC neurons have well-characterized receptive fields for individual sound features such as sound frequency, intensity, and location, growing evidence suggests that some neurons also use multiplexing to encode sound feature combinations. Here, we performed in vivo juxtacellular recordings in awake, head-fixed mice to examine how individual IC neurons and neuronal populations encode the speed, direction, and frequency range of frequency-modulated sweeps. To understand the strategies used by neurons to represent different sound features, we trained a support vector machine to decode sound features from different parameters of the spike train, including the firing rate, spike times relative to stimulus onset, distribution of inter-spike intervals, and first spike latency. We found that many IC neurons multiplex features of frequency-modulated (FM) sweeps using distinct temporal coding strategies rather than simple changes in mean firing rate, and that these feature representations are interdependent, yielding a combinatorial encoding of sound features within individual neurons. Accordingly, using static receptive fields for sweep frequency or direction alone yielded poor predictions of neuron responses to vocalizations that contain simple frequency changes. Lastly, we showed that encoding strategies varied across individual neurons, resulting in a highly informative population code for FM sweep parameters. Together, our results suggest that multiplexing is a common mechanism used by IC neurons to represent complex sound features.

neuroscience↗

Neuropeptide Y signaling regulates recurrent excitation in the auditory midbrain

Neuropeptides play key roles in shaping the organization and function of neuronal circuits. In the inferior colliculus (IC), which is located in the auditory midbrain, Neuropeptide Y (NPY) is expressed by a large class of GABAergic neurons that project locally as well as outside the IC. The IC integrates information from numerous auditory nuclei making the IC an important hub for sound processing. Most neurons in the IC have local axon collaterals, however the organization and function of local circuits in the IC remains largely unknown. We previously found that neurons in the IC can express the NPY Y1 receptor (Y1R+) and application of the Y1R agonist, [Leu31, Pro34]-NPY (LP-NPY), decreases the excitability of Y1R+ neurons. To investigate how Y1R+ neurons and NPY signaling contribute to local IC networks, we used optogenetics to activate Y1R+ neurons while recording from other neurons in the ipsilateral IC. Here, we show that 78.4% of glutamatergic neurons in the IC express the Y1 receptor, providing extensive opportunities for NPY signaling to regulate excitation in local IC circuits. Additionally, Y1R+ neuron synapses exhibit modest short-term synaptic plasticity, suggesting that local excitatory circuits maintain their influence over computations during sustained stimuli. We further found that application of LP-NPY decreases recurrent excitation in the IC, suggesting that NPY signaling strongly regulates local circuit function in the auditory midbrain. Together, our data show that excitatory neurons are highly interconnected in the local IC and their influence over local circuits is tightly regulated by NPY signaling.

neuroscience↗

GluN2D-containing NMDA receptors enhance temporal integration in VIP neurons in the inferior colliculus

Along the ascending auditory pathway, there is a broad shift from temporal coding, which is common in the lower auditory brainstem, to rate coding, which predominates in auditory cortex. This temporal-to-rate transition is particularly prominent in the inferior colliculus (IC), the midbrain hub of the auditory system, but the mechanisms that govern how individual IC neurons integrate information across time remain largely unknown. Here, we report the widespread expression of Glun2c and Glun2d mRNA in IC neurons. GluN2C/D-containing NMDA receptors are relatively insensitive to voltage-dependent Mg2+ block, and thus can conduct current at resting membrane potential. Using in situ hybridization and pharmacology, we show that VIP neurons in the IC express GluN2D-containing NMDA receptors that are activatable by commissural inputs from the contralateral IC. In addition, GluN2C/D-containing receptors have much slower kinetics than other NMDA receptors, and we found that GluN2D-containing receptors facilitate temporal summation of synaptic inputs in VIP neurons. In a model neuron, we show that a GluN2C/D-like conductance interacts with the passive membrane properties of the neuron to alter temporal and rate coding of stimulus trains. Consistent with this, we show in vivo that blocking GluN2C/D-containing receptors decreases both the spontaneous firing rate and the overall firing rate elicited by amplitude-modulated (AM) sounds in many IC neurons. These results suggest that GluN2C/D-containing NMDA receptors influence rate coding for auditory stimuli in the IC by facilitating the temporal integration of synaptic inputs. Significance statementNMDA receptors are critical components of most glutamatergic circuits in the brain, and the diversity of NMDA receptor subtypes yields receptors with a variety of functions. We found that many neurons in the auditory midbrain express GluN2C and/or GluN2D NMDA receptor subunits, which are less sensitive to Mg2+ block than the more commonly expressed GluN2A/B subunits. We showed that GluN2C/D-containing receptors conducted current at resting membrane potential and enhanced temporal summation of synaptic inputs. In a model, we show that GluN2C/D-containing receptors provide additive gain for input-output functions driven by trains of synaptic inputs. In line with this, we found that blocking GluN2C/D-containing NMDA receptors in vivo decreased both spontaneous firing rates and firing evoked by amplitude-modulated sounds.

neuroscience↗

Teaching Python for Data Science: Collaborative development of a modular & interactive curriculum

We are bioinformatics trainees at the University of Michigan who started a local chapter of Girls Who Code to provide a fun and supportive environment for high school women to learn the power of coding. Our goal was to cover basic coding topics and data science concepts through live coding and hands-on practice. However, we could not find a resource that exactly met our needs. Therefore, over the past three years, we have developed a curriculum and instructional format using Jupyter notebooks to effectively teach introductory Python for data science. This method, inspired by The Carpentries organization, uses bite-sized lessons followed by independent practice time to reinforce coding concepts, and culminates in a data science capstone project using real-world data. We believe our open curriculum is a valuable resource to the wider education community and hope that educators will use and improve our lessons, practice problems, and teaching best practices. Anyone can contribute to our educational materials on GitHub.

scientific communication and education↗