DOI: 10.5061/dryad.kkwh70sct
title: Intermittent rate coding and cue-specific neuronal ensembles support working memory

description: Persistent, memorandum-specific neuronal spiking activity has long been
 hypothesized to underlie working memory. However, emerging evidence
 suggests a possible role for ‘activity-silent’, synaptic mechanisms. This
 issue remains controversial because evidence for either view has largely
 relied on datasets that fail to capture single-trial population dynamics
 or on indirect measures of neuronal spiking. We addressed this by
 examining the dynamics of mnemonic information on single trials obtained
 from large, local populations of lateral prefrontal neurons recorded
 simultaneously in monkeys performing a working memory task. 
 Here, we show that mnemonic information does not persist in the spiking
 activity of neuronal populations during memory delays, but instead
 alternates between coordinated ‘On’ and ‘Off’ states. At the level of
 single neurons, Off states are driven both by a loss of selectivity for
 memoranda and a return of firing rates to spontaneous levels. Further
 exploiting the large-scale recordings, we show that mnemonic information
 is available in the patterns of functional connections among neuronal
 ensembles during Off states. Our results suggest that intermittent periods
 of memoranda-specific spiking coexist with synaptic mechanisms to support
 working memory. 
description: Subjects Three adult male
 rhesus monkeys (<em>Macaca mulatta</em>) participated in the
 experiment. Monkey A, H, and J weighed 11, 14, and 12 kg, respectively.
 All surgical and experimental procedures were approved by the Stanford
 University Institutional Animal Care and Use Committee and were in
 accordance with the policies and procedures of the National Institutes of
 Health. Behavioral
 task                          Stimuli were
 presented on a VIEWPixx3D monitor positioned at a viewing distance of 60
 cm using Psychtoolbox and MATLAB (MathWorks). Eye position was monitored
 at 1kHz using an Eyelink 1000 eye-tracking system (SR Research). On each
 trial, the animals were presented with a cue at one of 8 possible
 locations and reported this location after a brief memory delay to receive
 a fluid reward. Cues were square frames (green for Monkey A, black for
 Monkey H, white for Monkey J) measuring 1 degree of visual angle on a side
 and presented at 5-7 degrees of eccentricity (depending on the
 session). Monkeys initiated behavioral trials by
 fixating a central fixation spot presented on a uniform gray background.
 After the monkeys maintained fixation for 600-800 ms (randomly selected on
 each trial), a cue appeared for 50 ms at one of 8 possible locations
 separated by 45 degrees around fixation. Cue presentation was followed by
 a delay period that varied randomly from 1400-1600 ms. After the delay
 period, the fixation spot disappeared, and the animal was presented with
 one of two possible response screens. On match-to-sample (MTS) trials, two
 targets appeared (filled blue circles, radius 1 DVA), one at the
 previously cued location, and the other at one of the 7 remaining non-cued
 locations. On memory-guided saccade (MGS) trials, no targets appeared. In
 either case, the animals received a juice reward for making an eye
 movement to within 5 degrees of visual angle (DVA) of the previously cued
 location and then maintaining fixation for 200 ms. MTS and MGS trials were
 randomly interleaved such that the animals could not predict the trial
 type. Monkey J was trained on and performed only the MGS task. The animals
 had to maintain their gaze within 3 DVA (monkey A) or 2 DVA (monkey H
 & J) from fixation throughout the trial until the response stage.
 The intertrial interval was 300-1000 ms after each correct response.
 Failures to acquire fixation, fixation breaks, and incorrect responses
 were not rewarded and were followed by a 2,000 ms intertrial
 interval. Surgical Procedures and
 Recordings Monkeys were implanted with a
 titanium headpost to immobilize the head and with a titanium chamber to
 provide access to the brain (see ref. 1 for full details). In a previous
 study, we identified the frontal eye field (FEF) based on its
 neurophysiological characteristics and the ability to evoke saccades with
 electrical stimulation at low currents. Here, we recorded from both area
 8, within and anterior to the FEF, and the principal sulcus (9/46) (Monkey
 A: area 8; Monkey H: 8 and 9/46; Monkey J; 9/46) using primate neuropixels
 probes. During each session, we pierced the dura using a screw-driven 21
 gauge pointed cannula and lowered a single probe through this cannula
 using a combination of custom 3D printed grids and motorized drives (NAN
 instruments). Probe trajectories spanned several cortical columns, as
 inferred from the broad distribution of preferred cue locations across
 neurons. Recordings were allowed to settle for ~30 minutes prior to the
 start of the experiment to mitigate drift. We configured probes to record
 from 384 active channels in a contiguous block, allowing dense sampling of
 neuronal activity along a 3.84 mm span. Activity was
 filtered and digitized activity at the headstage (300 Hz high-pass filter,
 30 kHz sampling frequency). Activity was monitored during experimental
 sessions and saved to disk using SpikeGLX (https://billkarsh.github.io/SpikeGLX/). Data Preprocessing Spiking in the action-potential band was identified and sorted offline using Kilosort3. As we were interested in population-level coding of memory, we analyzed both putative single- and multi-unit clusters identified by Kilosort. Spike times were aligned to a digital trigger on each trial indicating cue onset and corrected for a lag in stimulus presentation estimated offline using photodiode measurements from the stimulus display and the timing of the cue-evoked response. Neurons that fired fewer than 1000 spikes in the ~3 hour experimental sessions were excluded from further analyses. Spikes times were binned with a width and timestep of 1 ms.
description: # Intermittent rate coding and cue-specific neuronal ensembles support
 working memory ### Overview --- This dataset consists of neural recordings
 from the lateral prefrontal cortex of rhesus macaques performing a spatial
 working memory task. The data are organized by *session*, a single ~1-3
 hour experiment during which the animal performed the task while we
 measured neuronal and behavioral responses. 10 sessions were recorded from
 monkey A, 8 from monkey H, 7 from monkey J. For more details, see the
 associated paper, [Panichello, Jonikaitis, Oh, Zhu, Trepka, & Moore
 (2023)](https://www.biorxiv.org/content/10.1101/2023.10.06.561121v1). ###
 Format --- The data for each session is saved as a set of variables in a
 MAT-file (*yymmdd*.mat). The variables are: * **spks**. *nTrials* x
 *nTimebins* x *nUnits boolean*. Spike rasters for each single- and
 multi-unit identified via spike sorting, aligned to cue onset on each
 trial. Spikes were binned with 1 ms resolution, from 500 ms before cue
 onset to 1450 ms after cue onset. * **tc**. *1 x nTimepoints double*.
 Center of each timebin, in ms relative to cue onset. * **cueAng**.
 *nTrials x 1 double*. Spatial angle of each cue, in radians, wrapped to
 pi. Angle is relative to the horizontal meridian and increases
 counter-clockwise (i.e., right = 0 rad, up = pi/2 rad). * **cueAngIdx**.
 *nTrials x 1 double*. Spatial angle of each cue, specified categorically
 using the integers 1 to 8. * **isCorr**. *nTrials x 1 boolean*. 1 if the
 animal responded correctly and received reward, 0 if the animal responded
 incorrectly. ### Data usage and citation --- Please inform Matt Panichello
 ([matt.panichello@gmail.com](mailto:matt.panichello@gmail.com)) and Tirin
 Moore ([tirin.moore@gmail.com](mailto:tirin.moore@gmail.com)) if you plan
 to use these data for your research. Please cite [Panichello, Jonikaitis,
 Oh, Zhu, Trepka, & Moore
 (2023)](https://www.biorxiv.org/content/10.1101/2023.10.06.561121v1) and
 the DOI for this dataset if you use these data in a publication.