Coexistence of state, choice, and sensory integration coding in barrel cortex LII/III

“Different codes could support the percep-tualrepresentationof the stimulus, includinga ratecode andtemporal codes 35,36 (e.g., periodicity of fi ring).”

“Besides, it was recently shown that brain-Article wide fl uctuations of activity were explained by face motion 9,80 but also pupil dilation in the awake animal 80 .”

“Two-photon laser scanning was controlled using the ScanImage software 2018 88 .”

“Movies were motion corrected and ROIs delineated using the routine from suite2p (Pachitariu et al. 2016) ROIs were manually curated and every visible cell with an event rate > 0.”

“4a), in agreement witha previous report 9 .”

“These studies found that trial-by-trial fl uctuations of neuronal activity in the visual areas predicted choices of the animal, i.e., display choice-related activity 5 .”

“net/addgene:100854 ; RRID:Addgene_100854) (Dana et al. 2016), or in combination with EGFP (2 mice pAAV.”

“It has been proposed that attention can selectively increase the representation of stimulus features relevant to the task 81 .”

“The columnar scale is particularly signi fi cant, as functional columns are considered the fundamental building blocks of the mammalian brain, prevalent across nearly all brain areas 53 .”

“Pioneering studies addressed that issue using two-choice dis-criminationtasks,whereprimateshadtojudgethemotiondirectionof a cloud of points 4,5 .”

“In our task, the engaged state is associated with a pupil contraction duringthepre-stimulusperiod,inlinewithrecentworkusingawhisker mediated 2AFC 16 , although at odds with earlier fi ndings 74,75 .”

“In our task, the engaged state is associated with a pupil contraction duringthepre-stimulusperiod,inlinewithrecentworkusingawhisker mediated 2AFC 16 , although at odds with earlier fi ndings 74,75 .”

“Thesepre-stimulusmarkersstrengthentheviewofadifferent brain state during phases of disengagement 25,26 , in which spontaneous activity of L2/3 is governed by synchronized, large amplitude oscillatory fl uctuations of activity.”

“In a situation when animals are asked to perform discrimination of multiple visual stimuli, the choice might actually be poorly predicted from the primary visual cortex activity 64 .”

“However, in this active mode, evoked activity is weaker and spatially confined to the principal barrel (Ferezou et al. 2007).”

“Recent manipulations, involving the activation of excitatory neurons or stimulus-selective sub-ensembles, have been shown to trigger learned behaviors 4,7,32,50 – 52 .”

“Area under the receiver operating curve (AUROC) is a standard metric to test whether a neuron’s activity is correlated to the choice of the subject (termed choice probability or CP(Britten et al. 1993; Crapse and Basso 2015).”

“These characteristics resemble in part to the active mode that displays, when compared to a quiescent awake mode, a depolarization of excitatory L2/3 cells 76,77 , and a suppression of the large subthreshold oscillations.”

“…single target neurons, in column size, functionally de fi ned ensembles; or using manipulation of different functional codes (e.g., temporal codes) 32,56,57 which may provide further insights into perception-related circuits and dynamics 58,59 .”

“Alternative methods for manipulation include activation of excitatory neurons or stimulus selective sub ensembles, which were shown to trigger learned behaviors (Salzman et al. 1990; Huber et al. 2008; Sachidhanandam et al. 2013; Musall et al. 2014; Ceballo et al. 2019; Marshel et al. 2019; Buetfering et al. 2022).”

“Instead, our results add to the growing evidence that choice coding lies in dimensions orthogonal to that of sensory representation, enabling multiplexing of information in different neuronal subspaces 55,69,70 .”

“Consistent with previous studies 17 – 19 , we found that a small fraction of neurons was highly responsive to tactile stimulation (~10%; Fig.”

“During the detection of near-threshold stimuli, activity in the primary sensory cortices conveys choice signals, in both primates 62,63 , and rodents 8 .”

“In the somatosensory system of the primate, similar approaches have revealed that choice-related activity arises from the secondary somatosensoryarea and ishigher in the decisional hierarchy 2,6 .”

“Previous studies have indicated that subjects use mainly the earliest temporal component of sensory activity to form their choice 7,71 , while the manipulation of later components correlating with decision signals have less causal in fl u-ence on them 7 and originates most likely from top-down…”

“However, the perturbation of activity homeostasis at a larger scale -including other brain areas-22 , might potentially be responsible for the impairment of behavior, independent of the manipulation of the sensory representation.”

“Another decoding strategy would be to reconstruct the frequency via maximum like-lihoodestimationusingBayesianinference 91 .”

“Different codes could support the percep-tualrepresentationof the stimulus, includinga ratecode andtemporal codes 35,36 (e.g., periodicity of fi ring).”

“This is, to our knowledge, the fi rst of these discrimination tasks using a variation of stimulation intensity, a critical parameter to study perception 15,29,30 .”

“5), similarly to what was found previously in the somatosensory system 67,68 .”

“These characteristics resemble in part to the active mode that displays, when compared to a quiescent awake mode, a depolarization of excitatory L2/3 cells 76,77 , and a suppression of the large subthreshold oscillations.”

“It is proposed to be bene fi cial in sharpening boundaries and information coding 46,47 .”

“…single target neurons, in column size, functionally de fi ned ensembles; or using manipulation of different functional codes (e.g., temporal codes) 32,56,57 which may provide further insights into perception-related circuits and dynamics 58,59 .”

“Previous studies have argued that neurometric coding performance by fi ring rate is closer to psycho-metricperformancethanthatof temporalcoding 33,37,38 .”

“2012), as well as cholinergic influence (Eggermann et al. 2014; Meir et al. 2018).”

“In other terms, the sensory code, rather than the activity in the area, should co-fl uctuate with the behavior 12 .”

“In the classical view of perceptually guided decision, sensory evidence builds gradually in decisional and motor areas 1,60,66 from pooling multiple sensory neurons that are weakly correlated with choice.”

“distance perturbation of neuronal homeostasis (off-target effects)(Otchy et al. 2015; Li et al. 2019).”

“Previous studies have argued that neurometric coding performance by fi ring rate is closer to psycho-metricperformancethanthatof temporalcoding 33,37,38 .”

“However, it may seem contradictory with more recent results in the murine model, showing a large difference in evoked activity between hits and misses before the onset of licking in a go/no-go paradigm, and a correlation between sensory and choice activity 8,61 .”

“A distinction between detection and discrimination has been made in non-human primate studies 65 .”

“In the classical view of perceptually guided decision, sensory evidence builds gradually in decisional and motor areas 1,60,66 from pooling multiple sensory neurons that are weakly correlated with choice.”

“More recently, research in rodents has identi fi ed choice-related activity forming already at the level of the primary somato-sensory area (S1) 7,8 , It is yet dif fi cult to conclude that the choice signals in S1 have a causal in fl uence on behavior and perception.”

“Suppression is proposed to be beneficial to sharpening boundaries and information coding (Li 1999; Angelucci et al. 2017).”

“…single target neurons, in column size, functionally de fi ned ensembles; or using manipulation of different functional codes (e.g., temporal codes) 32,56,57 which may provide further insights into perception-related circuits and dynamics 58,59 .”

“…single target neurons, in column size, functionally de fi ned ensembles; or using manipulation of different functional codes (e.g., temporal codes) 32,56,57 which may provide further insights into perception-related circuits and dynamics 58,59 .”

“The widespread cortical activity related to the onset of facial movement 9,10 — including in sensory areas — renders ambiguous the signals associated with choice if sensory integration and motor response are temporally overlapping.”

“5), similarly to what was found previously in the somatosensory system 67,68 .”

“Few studies required mice to discriminate neighboring whiskers 27,28 .”

“This is, to our knowledge, the fi rst of these discrimination tasks using a variation of stimulation intensity, a critical parameter to study perception 15,29,30 .”

“During detection of near threshold stimuli, activity in the primary sensory cortices convey choice signals, in both primates (Palmer et al. 2007; van Vugt et al. 2018), and rodents (Yang et al.”

“Few studies required mice to discriminate neighboring whiskers 27,28 .”

“Optogenetic wide fi eld stimulation was combined with two-photon functional imaging 21 (Fig.”

“Suppression is generally thought to be at least partially cortical dependent 39,45 .”

“This preprocessing strategy and criteria were optimized from the freely available jRGE-CO1a dataset from the CRCNS website 84 to match the state-of-the-art algorithmic performance in event detection 90 .”

“Alternative methods for manipulation include activation of excitatory neurons or stimulus selective sub ensembles, which were shown to trigger learned behaviors (Salzman et al. 1990; Huber et al. 2008; Sachidhanandam et al. 2013; Musall et al. 2014; Ceballo et al. 2019; Marshel et al. 2019; Buetfering et al. 2022).”

“…discrimination of neighboring inputs As described in previous work, we found that evoked activity in L2/3 displays a somatotopic organization with salt-and-pepper whisker tuning of single neurons 20,31 , is sparsely distributed in the population 17 – 19 and adapts rapidly in most neurons 18,32 .”

“We observed multi-whisker integration, found to be mostly suppressive (as previously reported 39 – 42 with the exception of some neurons responding supralinearly to multi-whisker stimuli 43,44 .”

“We observed multi-whisker integration, found to be mostly suppressive (as previously reported 39 – 42 with the exception of some neurons responding supralinearly to multi-whisker stimuli 43,44 .”

“Previous studies have argued that neurometric coding performance by fi ring rate is closer to psycho-metricperformancethanthatof temporalcoding 33,37,38 .”

“We also observed a suppression of slow oscillatory activity 26 .”

“It has thus been proposed that more complex designs, such as two alternative forced choice tasks (2AFC) featuring a delayed response, are needed to disentangle choice from these other sources of modulation 11 .”

“While our study speci fi cally addresses earlysensory representationinthesomatosensory system 54 , its implications may extend to other perceptual representations in areas displaying cortical maps.”

“…single target neurons, in column size, functionally de fi ned ensembles; or using manipulation of different functional codes (e.g., temporal codes) 32,56,57 which may provide further insights into perception-related circuits and dynamics 58,59 .”

“Besides we observed multi-whisker integration, found to be mostly suppressive (as previously reported in Mirabella et al. 2001; Jacob et al. 2008; Pluta et al. 2017; Laboy-Juárez et al. 2019) with the exception of some neurons responding supralinearly to multi-whisker stimuli (Lyall et al.”

“This is, to our knowledge, the fi rst of these discrimination tasks using a variation of stimulation intensity, a critical parameter to study perception 15,29,30 .”

“This procedure has been described in detail in a previous article (Mayrhofer et al. 2013).”

“Besides we observed multi-whisker integration, found to be mostly suppressive (as previously reported in Mirabella et al. 2001; Jacob et al. 2008; Pluta et al. 2017; Laboy-Juárez et al. 2019) with the exception of some neurons responding supralinearly to multi-whisker stimuli (Lyall et al.”

“2012), as well as cholinergic influence (Eggermann et al. 2014; Meir et al. 2018).”

“In summary, the task and optical techniques presented here allow for a fl exible combination of manipulative and correlative approaches, necessary for understanding the substrate of perception and decision making 12,83 .”

“Area under the receiver operating curve (AUROC, see methods) is a standard metric to test whether a neuron ’ s activity is correlated to the choice of the subject (termed choice probability or CP 23,24 .”

“As frequencies are directly proportional to the mean speed de fl ection of the whisker, frequencies also represent the intensity of stimulation 13 .”

“We observed multi-whisker integration, found to be mostly suppressive (as previously reported 39 – 42 with the exception of some neurons responding supralinearly to multi-whisker stimuli 43,44 .”

“…have indicated that subjects use mainly the earliest temporal component of sensory activity to form their choice 7,71 , while the manipulation of later components correlating with decision signals have less causal in fl u-ence on them 7 and originates most likely from top-down modulation 70,72,73 .”

“…discrimination of neighboring inputs As described in previous work, we found that evoked activity in L2/3 displays a somatotopic organization with salt-and-pepper whisker tuning of single neurons 20,31 , is sparsely distributed in the population 17 – 19 and adapts rapidly in most neurons 18,32 .”

“In our task, the engaged state is associated with a pupil contraction duringthepre-stimulusperiod,inlinewithrecentworkusingawhisker mediated 2AFC 16 , although at odds with earlier fi ndings 74,75 .”

“…have indicated that subjects use mainly the earliest temporal component of sensory activity to form their choice 7,71 , while the manipulation of later components correlating with decision signals have less causal in fl u-ence on them 7 and originates most likely from top-down modulation 70,72,73 .”

“Consistent with previous studies 17 – 19 , we found that a small fraction of neurons was highly responsive to tactile stimulation (~10%; Fig.”

“Increasing stimulation frequency of a single whisker increases monotonically population response 18,33,34 .”

“…et al., 2010; Miyashita and Feldman, 2012; Feldmeyer et al., 2013; Guo et al., 2014a; Burgess et al., 2017; Fassihi et al., 2017; Chakrabarti and Schwarz, 2018; Hong et al., 2018; Odoemene et al., 2018; Ryan et al., 2022; Waiblinger et al., 2022; Diamond and Toso, 2023; Gardères et al., 2024).”

“…indicate that the primary sensory cortex not only retains relatively weak and sparse choice-related activity, as it was shown previously (10, 11, 19–25), but also, in our naturalistic behavioral task, directly participates in a categorical coding of all-or-none DV into which the majority of neural…”

“The results of these columnar computations are then broadcast to the rest of the brain, shaping behavior and sensory decisions (60– 62).”

“The results of these columnar computations are then broadcast to the rest of the brain, shaping behavior and sensory decisions 60 – 62 .”

“…our architecture strategically incorporates 8 excitatory neuron subtypes and 37 documented projection pathways from barrel cortex studies [37, 44, 12, 14, 31, 39, 27, 58], including projections from Layer 4 (L4) to L2/3 neurons and feedback connections from L5/6 to L4 neurons, among others (Fig.”