Origins of choice-related activity in mouse somatosensory cortex

“GCaMP6s 26 was expressed under the human synapsin-1 promoter following infection with recombinant adeno-associated virus (serotype 2/1, Syn.”

“Neurons with higher choice probability tend to be more sensitive to the stimulus (e.g. have lower “neurometric” thresholds) 1,6,10,12,37 .”

“Intracellular recording, recently possible in task-performing animals 19,32,33 , reveals the subthreshold membrane potential (V m ) dynamics that govern spiking.”

“In addition, computational work suggests that choice probability is shaped by patterns of inter-neuronal correlations, which may differ across perceptual tasks 3,7,36,46,47 .”

“Additional long-range inputs to S1 may also play a role, for instance neuromodulatory 40 axons, projections from the higher-order posteromedial thalamic nucleus 41 , or top-down projections from other motor-sensory areas 34,42,43 .”

“The smaller piece (Fisher; number 2 thickness) was fitted into the craniotomy and the larger piece (number 1.5 thickness) was glued to the bone surrounding the craniotomy 48 .”

“If spike rate detect probability and stimulus probability are both determined by subthreshold stimulus sensitivity (V rev − V spike ), they should be correlated (cf. 1,6,10,12,37,38 ).”

“Silent cells 31 which spiked very sparsely or did not respond to whisker stimulation were avoided during the process of establishing the recording.”

“We did this to understand variability in cortical spike rate, which has been widely observed to predict choice 1,2,4,6–11,13,14 .”

“This may have encouraged heightened levels of vigilance and/or affected neuromodulatory 40,50 systems that can alter neural variability.”

“Intracellular recording, recently possible in task-performing animals 19,32,33 , reveals the subthreshold membrane potential (V m ) dynamics that govern spiking.”

“This supports a prior finding of top-down contributions to choice probability in monkey visual cortex 8 , and is consistent with the stronger choice-related activity in S2 compared with S1 of monkeys 14 .”

“To investigate sources of choice-related activity other than feedforward 17 drive (cf. 8 ), we used two-photon calcium imaging during behavior to monitor top-down axons 34 projecting from secondary somatosensory (S2) cortex to layer 1 of S1 (Fig.”

“We did this to understand variability in cortical spike rate, which has been widely observed to predict choice 1,2,4,6–11,13,14 .”

“The extent to which different sensory brain areas show choice-related activity, and the role of task features, is an active topic of investigation 9,11,12,44,45 .”

“Under isoflurane (1–2%), a craniotomy (~1 mm diameter) was made over the left hemisphere, centered at 1.8 mm posterior to bregma, 1.5 mm lateral to midline 54 .”

“Intracellular recording, recently possible in task-performing animals 19,32,33 , reveals the subthreshold membrane potential (V m ) dynamics that govern spiking.”

“Choice-related activity (choice or detect probability > 0.5) has been observed in multiple sensory brain areas, including monkey extrastriate 1,2,4,6–10 and primary 11,12 visual cortex, monkey while mice performed the detection task using the single whisker in the neuron’s receptive field (Fig.”

“In the context of detection tasks, the same quantity is often referred to as “detect probability” (DP) 4,5 ; we adopt this convention here.”

“We did this to understand variability in cortical spike rate, which has been widely observed to predict choice 1,2,4,6–11,13,14 .”

“Additional long-range inputs to S1 may also play a role, for instance neuromodulatory 40 axons, projections from the higher-order posteromedial thalamic nucleus 41 , or top-down projections from other motor-sensory areas 34,42,43 .”

“Additional long-range inputs to S1 may also play a role, for instance neuromodulatory 40 axons, projections from the higher-order posteromedial thalamic nucleus 41 , or top-down projections from other motor-sensory areas 34,42,43 .”

“Titanium headposts were implanted for head fixation 22 .”

“7b) 18–21 .”

“In addition, computational work suggests that choice probability is shaped by patterns of inter-neuronal correlations, which may differ across perceptual tasks 3,7,36,46,47 .”

“This transient difference was also apparent in a measure of thalamic synchrony 29,30 (Supplementary Fig.”

“In addition, computational work suggests that choice probability is shaped by patterns of inter-neuronal correlations, which may differ across perceptual tasks 3,7,36,46,47 .”

“The extent to which different sensory brain areas show choice-related activity, and the role of task features, is an active topic of investigation 9,11,12,44,45 .”

“However, computational 46 and theoretical work 38,47 has shown that multiple factors, including both read-out strategies 47 and inter-neuronal correlations, can shape choice probability 3,7,36 .”

“This transient difference was also apparent in a measure of thalamic synchrony 29,30 (Supplementary Fig.”

“V rev is thus an intracellular measure of stimulus sensitivity 18–20 .”

“In addition, computational work suggests that choice probability is shaped by patterns of inter-neuronal correlations, which may differ across perceptual tasks 3,7,36,46,47 .”

“3c) 28 .”

“The extent to which different sensory brain areas show choice-related activity, and the role of task features, is an active topic of investigation 9,11,12,44,45 .”

“Neurons with higher choice probability tend to be more sensitive to the stimulus (e.g. have lower “neurometric” thresholds) 1,6,10,12,37 .”

“More sophisticated analyses, such as those based on population decoding 48,49 or precise knowledge of network oscillations 24 , might reveal an influence of pre-stimulus brain state on perceptual choice.”

“Correlations between sensory neuron spike trains and behavioral choices are often quantified using “choice probability” 1 or “detect probability” 4,5 , the probability with which an ideal observer could predict behavioral choice based on neural activity evoked by identical stimuli.”

“Trigeminal ganglion neurons had low baseline spike rates that did not differ between Hit and Miss trials (0.77 ± 20.1 vs 0.62 ± 28.4 Hz [median ± interquartile range], p = 0.55, two-tailed sign test, n = 17; Fig.”

“Microneurography studies in humans 16 (and a recent study in monkeys: 39 ) have demonstrated the power of combining psychophysics with single-unit recording from primary afferents.”

“The extent to which different sensory brain areas show choice-related activity, and the role of task features, is an active topic of investigation 9,11,12,44,45 .”

“Microneurography studies in humans 16 (and a recent study in monkeys: 39 ) have demonstrated the power of combining psychophysics with single-unit recording from primary afferents.”

“The distribution of behavioral choice and choice-related activity across sensorimotor pathways (Nienborg et al., 2012; Yang et al., 2016) has been proposed within the non-hierarchical framework of decision-making to be a more rapid and flexible mechanism for incorporating internal, proprioceptive, and environmental co…”

“Anatomical, electrophysiological, and imaging studies have demonstrated distinct local and large-scale connectivity associated with varied feature encoding even for neighboring neurons in a single region 6–10 .”

“Thus, consistent with previous reports (Chen et al., 2016; Yang et al., 2016), sensory-related posterior areas S1BC, S2, and RL encode choice shortly after touch for both behavioral strategies.”

“The late (100–200 ms) sensory-evoked response was significantly smaller for Miss trials in all areas, including wS1, consistent with previous findings (Sachidhanandam et al., 2013; Yang et al., 2016; Yamashita and Petersen, 2016).”

“Despite this promiscuous connectivity, some studies suggest that the PV populationmay preferentially inhibit specific PC subtypes (Ye et al., 2015), though reports in L5 conflict over whether IT or PT cells receive more inhibition (Fariñas and DeFelipe, 1991; Lee et al., 2014; Rock and Apicella,…”

“We find that S2S1 neurons exhibit prominent licking and decision-related activity, which is in line with recent evidence that behavior-related activity in S1 can be inherited from S2 (Yang et al., 2016).”

“…Etemadi et al., 2016 0.01 / 0.1 10 μm/s / 100 μm/s rat C bundles of parylene C coated platinum electrodes 54 Leiser and Moxon, 2006 0.01 / 0.1 10 μm/s / ~100 μm/s rat A epoxylite- insulated tungsten microelectrodes 55 Yang et al., 2016 0.01 / 0.05 - 0.1 10 μm/s / 50 -…”

“In a simple task, water-restricted head-fixed mice report the detection of a target sensory stimulus—a brief whisker deflection—by licking a water spout to obtain a small drop of water as a reward (Miyashita and Feldman, 2013; Sachidhanandam et al., 2013; Yang et al., 2016).”

“Adult mice (6-18 weeks old) were implanted with titanium headposts (Yang et al., 2016).”

“Consistent with such a hypothesis involving reciprocal excitation between S1 and S2, axons from S2 innervating S1 were found to exhibit strong task-related hit vs miss modulation in a closely-related whisker detection task (Yang et al., 2016).”

“Blind whole-cell recordings of the Vm correlates of tactile sensory perception have also been investigated in mice trained to lick a reward spout in response to detected whisker stimuli (Sachidhanandam et al., 2013; Zagha et al., 2015; Yang et al., 2016).”

“This initial processing was essential as shown by optogenetic inactivation (Figure 7), and therefore wS1 and wS2 appear to form the cortical starting points for task execution, in agreement with previous studies of whisker detection tasks without a delay period (Kwon et al., 2016; Kyriakatos et al., 2017; Le Merre et…”

“We used receiver operating characteristic (ROC) analysis [57] to identify neurons responding to either novel or familiar texture, or both.”

“, 2016), which might be supported through reciprocal excitation of S1 and S2 (Kwon et al., 2016; Yang et al., 2016).”

“Neuronal activity in wS1 has been shown to be involved in whisker-based decision-making tasks (Guo et al., 2014; Miyashita and Feldman, 2013; Sachidhanandam et al., 2013; Yang et al., 2016), thus providing a well-defined starting point for cortical processing of whisker-related information.”

“Activity related to perceptual decisions in various sensory cortices has been widely reported in past decades (Britten et al., 1996; Celebrini and Newsome, 1994; Cohen and Newsome, 2009; Liu et al., 2013; Nienborg and Cumming, 2009; Nienborg et al., 2012; Romo et al., 2002; Tsunada et al., 2016; Yang et al., 2016).”

“Heterogeneous Representation of Task-Related Information Although whisker S1 and S2 have been observed to encode stimulus and choicerelated activity (Chen et al., 2016; Kwon et al., 2016; Yamashita and Petersen, 2016; Yang et al., 2016), the extent to which more complex, context-modulated information is also present h…”

“Given the strong modulation of wS2 neurons and of their feedback to wS1 during perceptual decisions (Chen et al., 2016; Kwon et al., 2016; Yang et al., 2016; Zuo et al., 2015), our data suggest that the S2L4 / S1 pathway may regulate wS1 feature sensitivity during behavior.”

“Nevertheless, this task appears to be more demanding and challenging for the mice to learn compared with tactile detection tasks without a rule switch (e.g., Aruljothi et al., 2020; Yang et al., 2016), as mice can typically perform the latter at >70% within 2 weeks of training.”

“Second, and perhaps related, it has been observed that barrel cortex neurons of mice, trained to detect single-whisker deflections, exhibit non-sensory driven spiking, which correlates with animal choice (Yang et al., 2015).”

“…to primary somatosensory cortex in humans (Jones et al., 2007; Auksztulewicz et al., 2012; Auksztulewicz and Blankenburg, 2013), mice (Kwon et al., 2016; Yang et al., 2016), and macaques (Cauller and Kulics, 1991), supporting the role of local recurrent processing for somatosensory awareness.”

“Generally, these signals are lacking in afferents (Yang et al., 2016; Yu et al., 2015) but begin to emerge and become stronger along the hierarchy of cortical stages, for example, from the primary sensory cortices to decision-related areas (de Lafuente and Romo, 2006; Hernández et al.”

“, 2016) and gets worse when multiple PV or somatostatin interneurons are optogenetically stimulated (Guo et al., 2014; Takahashi et al., 2016; Yang et al., 2016).”

“This is in agreement with previous data from membrane potential recordings in S1 during closely related whisker detection tasks.(33,34,36) Within the imaged portion of the contralateral dorsal neocortex, the largest hit versus miss differences were located in the frontal cortex in regions surrounding whisker M1, locat…”

“Post-stimulus activity was calculated using a 200 ms window starting 20 ms after stimulus onset, before licking responses (Yang et al., 2016).”

“, 2013), including secondary somatosensory cortex (S2) (Yang et al., 2016; Kwon et al., 2016), posterior parietal cortex (PPC) (Mohan et al.”

“S1 and S2 are the corticalorigins of perceptual activity during sensory decisions 29,35 – 37 .”

“Such a mechanism might account for the early transformation from stimulus intensity to detection probability that we observed in SI and in fact, previous research on somatosensory target detection suggests that stimulus awareness is best captured in recurrent interactions between SI and SII (Auksztulewicz et al., 2012…”

“…51 (Campagner et al., 2016; Crochet and Petersen, 2006; Curtis and Kleinfeld, 2009; Fee et al., 52 1997; Hires et al., 2015; Khatri et al., 2009; Leiser and Moxon, 2007; Moore et al., 2015; 53 Severson et al., 2017; Szwed et al., 2003; Wallach et al., 2016; Yu et al., 2006; Yu et al., 2016).”

“In rodent S1, many L2/3 neurons exhibit choice-related spiking in near-threshold detection tasks [11,49].”

“Furthermore, trial-to-trial observation of neuronal activity reveals a high 469 degree of choice-related information in vS1 neurons (von Heimendahl et al., 2007; 470 Takahashi et al., 2016; Yang et al., 2016).”

“Orientation coding and sequence consistency are uncorrelated It has been reported that neuronal population representations of stimulus features are more accurate during the detection of stimuli (Montijn et al., 2015; Yang et al., 2016).”

“, 2014) bears similarity to the observations made in the cortex (Gilad et al., 2018; Guo et al., 2019; Harvey et al., 2012; Pho et al., 2018; Siegel et al., 2015; Yang et al., 2016), indicating the intimate involvement of thalamocortical loops during learning.”

“This system interacts rapidly with the experimental subjects and therefore provides high-time-resolution measurements of the behavioral events to enable coordination with other recording devices such as electrophysiology and imaging (Erlich et al., 2011; Brunton et al., 2013; O’Connor et al., 2013; Yang et al., 2016).”

“[32] Other studies have considered that choice-related activity might arise from decision feedback[47,49,50].”

“Current technological innovations have further advanced our understanding of how neurons interact in dynamic circuits and how neural activity patterns are involved in behavioral and cognitive processes, such as sensory representation, motor control, or decision-making [10 – 12].”

“Thus, our 445 results, together with other studies on the role of S1 in decision making (47, 48), support the role 446 S1B L2/3 neurons’ population dynamics in integrating peripheral derived diverse somatosensory 447 stimuli and steering the brain states toward different actions.”

“However, another large body of literature has demonstrated that sensory processing in even the earliest sensory cortices can be modified by various external and internal contexts, including motor feedback, temporal statistics, learned associations, and attentional control (Roelfsema and de Lange, 2016; Gilbert and Sig…”

“Choice-related responses in S1S2 neurons appear to be inherited from S2 (Chen et al., 2016; Kwon et al., 2016; Yang et al., 2016).”

“S1 and S2 are the cortical origins of perceptual activity during sensory decisions (Kwon et al., 2016; Yang et al., 2016; Esmaeili et al., 2021; Buetfering et al., 2022).”

“However, our study and other studies of the mouse whisker system also show choice encoding in S1 (Sachidhanandam et al., 2013; Yang et al., 2015; Kwon et al., 2016; Aruljothi et al., 2020).”

“This notion has been strengthened by a recent report demonstrating choice-related modification of stimulus-evoked response in the medial ventroposterior (VPm) thalamus, the tactile first-order stimulus of the whisker-related tactile system in rodents (Yang et al., 2016).”

“Trials were also considered impulsive when mice licked within the first 100 ms window from stimulus onset (Mayrhofer et al., 2013; Yang et al., 2016).”

“…(Britten et al., 1996; Haefner et al., 2013; Wimmer et al., 2015), but there is growing evidence that top-down (feedback) signals make important contributions to the presence of CPs (Nienborg and Cumming, 2009; Wimmer et al., 2015; Cumming and Nienborg, 2016; Kwon et al., 2016; Yang et al., 2016).”

“…in part by showing that the correlated noise in populations of sensory neurons changes with attentional state or other task demands (Cohen and Newsome, 2008; Cohen and Maunsell, 2009; Mitchell et al., 2009; Nienborg and Cumming, 2009; Ruff and Cohen, 2014; Yang et al., 2016; Bondy et al., 2018).”

“Previouslyde fi ned somatosensory cortical circuits which mitigate sensorimotor action originate fromthe primary somatosensorycortex (S1) 4,77 and exert action via direct or indirect spinal connections or through connections with the primary motor cortex (M1) 78 , or from S2 to S1/M1 13,14,40 .”

“The needle was retracted slowly 5 minutes after the injection was completed and a cranial window (made from a 3 mm circular glass cover slip glued onto a 4 mm circular glass cover slip with optical glue NOR-61, Norland Optical Adhesive) was press-fit into the craniotomy and sealed in place with…”

“The detection of perception-related activity in mouse S1 is consistent with previous studies showing that S1 neurons signal tactile perceptual choices and causally contribute to driving the subjective percept [17,18,37].”

“38,44,45 ‘‘Vi-sual sensitivity’’ was defined as the area under the ROC curve (AUC) minus 0.5.”

“We used receiver operating characteristic (ROC) analysis to measure how well the activity of an individual neuron can detect stimulus presence on a trial-by-trial basis 40,46,47 .”

“Choice-related activity in the superficial layers has been reported in go/no-go somatosensory, 9,25 auditory, 26 and visual tasks, 27 as well as in two-alternative auditory 28 and somatosensory 29 discrimination tasks.”

“…the stereotypical animal behavior observed in this task, brain dynamics may be sensitive to task performance levels but also to the different behavioral strategies developed by animals (Nienborg et al., 2012; Sachidhanandam et al., 2013; Manita et al., 2015; Siegel et al., 2015; Yang et al., 2015).”