Search bioRxiv⌕ Search

Biology subjects

Hires, S. A.

Publications and source records attributed to Hires, S. A..

4 recordsLinked to original sources

Cell-type specialization of layer 5 excitatory neurons in tactile behavior

Layer 5 is the canonical output layer of sensory cortex. The two most numerous neural constituents of Layer 5 are pyramidal tract (PT) and intratelencephalic (IT) neurons. These output cell classes combine diverse sets of inputs and project to distinct locations across the brain, suggesting differing roles in sensory information processing. Here, we investigated the representation of touch and whisker motion in these two cell types within primary somatosensory cortex (S1) using optogenetically targeted single unit electrophysiology during whisker-guided object localization. PT neurons (N = 32) had much higher spike rates than IT (N=26) during behavior. Individual members of both were modulated by, but average population firing rates were stable between quiet and whisking periods. PT neurons showed greater absolute spike rate changes, but less relative modulation than IT neurons to whisking kinematic features. Touch-excited PT (N = 18) and IT neurons (N = 8) rapidly adapted to active touch. Both populations encoded the azimuthal position of touched objects, with IT neurons more sharply tuned to position. However, position was more precisely decodable from PT population activity, due to greater evoked spikes per touch. A consequence of these characteristics is that PT neurons, with their higher firing rates, may be more effective participants in rate-based neural codes, while IT neurons, with their sharp modulation, may be more effective in timing or synchrony-based codes.

neuroscience↗

WhACC: Whisker Automatic Contact Classifier with Expert Human-Level Performance

The rodent vibrissal system remains pivotal in advancing neuroscience research, particularly for studies of cortical plasticity, learning, decision-making, sensory encoding and sensorimotor integration. While this model system provides notable advantages for quantifying active tactile input, it is hindered by the labor-intensive process of curating touch events across millions of video frames. Even with the aid of automated tools like the Janelia Whisker Tracker, millisecond-accurate touch curation often requires >3 hours of manual review / million video frames. We address this limitation by introducing Whisker Automatic Contact Classifier (WhACC), a python package designed to identify touch periods from high-speed videos of head-fixed behaving rodents with human-level performance. For our model design, we train ResNet50V2 on whisker images and extract features. Next, we engineer features to improve performance with an emphasis on temporal consistency. Finally, we select only the most important features and use them to train a LightGBM classifier. Classification accuracy is assessed against three expert human curators on over one million frames. WhACC shows pairwise touch classification agreement on 99.5% of video frames, equal to between-human agreement. Additionally, comparison between an expert curator and WhACC on a holdout dataset comprising nearly four million frames and 16 single-unit electrophysiology recordings shows negligible differences in neural characterization metrics. Finally, we offer an easy way to select and curate a subset of data to adaptively retrain WhACC. Including this retraining step, we reduce human hours required to curate a 100 million frame dataset from [~]333 hours to [~]6 hours.

animal behavior and cognition↗

Directed motor actions and choice signalling drive cortical acetylcholine dynamics.

Numerous cognitive functions including attention and learning are influenced by the dynamic patterns of acetylcholine release across the brain. How acetylcholine mediates these functions in cortex remains unclear, as the relationship between cortical acetylcholine and behavioral events has not been precisely measured across task learning. To dissect this relationship, we quantified motor behavior and sub-second acetylcholine dynamics in primary somatosensory and auditory cortex during rewarded sensory detection and discrimination tasks. We found that acetylcholine dynamics were directly attributable to goal-directed actions (whisker motion and licking), rather than delivery of sensory cues or rewards. As task performance improved across training, acetylcholine release associated with the first lick in a trial was strongly and specifically potentiated. These results show that acetylcholine dynamics in sensory cortex are driven by directed motor actions to gather information and act upon it.

neuroscience↗

An automated homecage system for multiwhisker detection and discrimination learning in mice

Automated, homecage behavioral training for rodents has many advantages: it is low stress, requires little interaction with the experimenter, and can be easily manipulated to adapt to different experimental condition. We have developed an inexpensive, Arduino-based, homecage training apparatus for sensory association training in freely-moving mice using multiwhisker air current stimulation coupled to a water reward. Animals learn this task readily, within 1-2 days of training, and performance progressively improves with training. We examined the parameters that regulate task acquisition using different stimulus intensities, directions, and reward valence. Learning was assessed by comparing anticipatory licking for the stimulus compared to the no-stimulus (blank) trials. At high stimulus intensities (>9 psi), animals showed markedly less participation in the task. Conversely, very weak air current intensities (1-2 psi) were not sufficient to generate rapid learning behavior. At intermediate stimulus intensities (5-6 psi), a majority of mice learned that the multiwhisker stimulus predicted the water reward after 24-48 hrs of training. Both exposure to isoflurane and lack of whiskers decreased animals ability to learn the task. Perceptual learning was assessed and following training at an intermediate stimulus intensity, perception was likely heightened as mice were able to transfer learning behavior when exposed to the lower stimulus intensity. Mice learned to discriminate between two directions of stimulation rapidly and accurately, even when the angular distance between the stimuli was <15 degrees. Switching the reward to a more desirable reward, aspartame, had little effect on learning trajectory. Our results show that a tactile association task in an automated homecage environment can be monitored by anticipatory licking to reveal rapid and progressive behavioral change. These Arduino-based, automated mouse cages enable high-throughput training that facilitate analysis of large numbers of genetically modified mice with targeted manipulations of neural activity.

neuroscience↗