Automated long-term recording and analysis of neural activity in behaving animals

Abstract

Addressing how neural circuits underlie behavior is routinely done by measuring electrical activity from single neurons in experimental sessions. While such recordings yield snapshots of neural dynamics during specified tasks, they are ill-suited for tracking single-unit activity over longer timescales relevant for most developmental and learning processes, or for capturing neural dynamics across different behavioral states. Here we describe an automated platform for continuous long-term recordings of neural activity and behavior in freely moving rodents. An unsupervised algorithm identifies and tracks the activity of single units over weeks of recording, dramatically simplifying the analysis of large datasets. Months-long recordings from motor cortex and striatum made and analyzed with our system revealed remarkable stability in basic neuronal properties, such as firing rates and inter-spike interval distributions. Interneuronal correlations and the representation of different movements and behaviors were similarly stable. This establishes the feasibility of high-throughput long-term extracellular recordings in behaving animals.

Cholinergic modulation of spatial learning, memory and navigation

“…Standard rodent navigation tasks do not provide fine grained behavioral information and present only limited cognitive challenge to rats and mice. While this was a constraint when animals had to be trained manually, the emergence of the rodent cognition field operating with high throughput automated assays (Brunton, Botvinick, & Brody, ; Dhawale et al., ; O'Connor et al., ) with psychometric training that allows controlling cognitive demand and testing well defined hypotheses will likely transform our understanding of spatial cognition. One example is the emergence and spread of rodent VR navigation systems in recent years (Aronov & Tank, ; Kaupert et al., ; Leinweber, Ward, Sobczak, Attinger, & Keller, ) allowing complicated navigation tasks.…”

High-density, long-lasting, and multi-region electrophysiological recordings using polymer electrode arrays

“…This approach allowed us to continuously track a substantial fraction of units across many days, despite the expected waveform variation 7 . An example of a unit that was tracked for the entire period is shown in Figure 4a-d, and on this shank, 24 of 41 clusters identified in the first 24-hour segment could be tracked for more than one week of recording ( Fig.…”

“…Firing rate stability in a well-learned task In the absence of external perturbations, the majority of single-neurons show stable responses when measured intermittently across days 7,[38][39][40] . Similar observations have been made from daily recordings in rodent mPFC during spatial behaviors from 60 units across 2 days, and 8 units across 6 days 41 , suggesting that rodent mPFC units show stable firing properties in the context of well-learned behaviors.…”

“…Conversely, long term, continuous recordings of small numbers of neurons were recently documented with a 64-channel tetrode-based system 7 , but this approach does not provide a clear path to recordings from much larger ensembles.…”

A normalized template matching method for improving spike detection in extracellular voltage recordings

“…Thus, high quality in both spike detection and clustering algorithms are critical to accurately measure single unit activity. Recent breakthroughs have significantly improved spike clustering procedures, greatly reducing the need of manual intervention and allowing recording of single unit activity in large neuronal populations over long periods of time [6][7][8] . Despite these advances, spike detection is still mostly done with a simple voltage threshold trigger, a method that can fail to detect spikes relative to background recording noise and during spatiotemporally dense population activity.…”