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Origins of choice-related activity in mouse somatosensory cortex.

Yang H, Kwon SE, Severson KS, O'Connor DH - Nat. Neurosci. (2015)

Bottom Line: Spike trains from primary mechanoreceptive neurons did not predict choices about identical stimuli.An intracellular measure of stimulus sensitivity determined which neurons converted choice-related depolarization into spiking.Our results reveal how choice-related spiking emerges across neural circuits and within single neurons.

View Article: PubMed Central - PubMed

Affiliation: The Solomon H. Snyder Department of Neuroscience and Brain Science Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

ABSTRACT
During perceptual decisions about faint or ambiguous sensory stimuli, even identical stimuli can produce different choices. Spike trains from sensory cortex neurons can predict trial-to-trial variability in choice. Choice-related spiking is widely studied as a way to link cortical activity to perception, but its origins remain unclear. Using imaging and electrophysiology, we found that mouse primary somatosensory cortex neurons showed robust choice-related activity during a tactile detection task. Spike trains from primary mechanoreceptive neurons did not predict choices about identical stimuli. Spike trains from thalamic relay neurons showed highly transient, weak choice-related activity. Intracellular recordings in cortex revealed a prolonged choice-related depolarization in most neurons that was not accounted for by feed-forward thalamic input. Top-down axons projecting from secondary to primary somatosensory cortex signaled choice. An intracellular measure of stimulus sensitivity determined which neurons converted choice-related depolarization into spiking. Our results reveal how choice-related spiking emerges across neural circuits and within single neurons.

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Choice-related activity in mouse primary somatosensory cortex(a) Tactile detection task based on deflections of a single whisker. (b) Trial structure. A tone alerted mice to the time of possible stimulus onset. On Go trials, the whisker was stimulated with a sinusoidal deflection (0.5 s, 20 or 40 Hz). Mice responded by licking or not licking within a 1.8 s response window. (c) Four trial types are possible, based on the stimulus condition (present/absent) and the response (lick/no lick). (d) Behavioral detection performance varied with deflection speed for a single whisker (thin black lines) and three whiskers deflected simultaneously (thin purple lines). Plot symbols indicate different mice (n = 3). Thick lines show mean performance across mice for deflection of one (black) or three (purple) whiskers. Gray plot symbol at top-right shows performance (n = 2 mice) with strong multi-whisker stimulation. Gray bracket indicates range of speeds used for electrophysiology and imaging experiments. (e) Two-photon calcium imaging of primary somatosensory (S1) cortex during the tactile detection task. Left: cranial window showing region expressing the genetically encoded calcium indicator GCaMP6s. Right: example two-photon image over S1 showing hundreds of individual layer 2/3 neurons (white). (f) Example activity (ΔF/F0) traces from a single neuron for two Hit (blue), two Miss (black) and two Correct Rejection (red) trials. Inset: early portion of traces, before the earliest behavioral reaction times, used to calculate “evoked” ΔF/F0. (g) Cumulative histograms showing mean ΔF/F0 for Hit (blue), Miss (black) and Correct Rejection (red) trials for each neuron (n = 1,746 neurons from 6 mice).
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Figure 1: Choice-related activity in mouse primary somatosensory cortex(a) Tactile detection task based on deflections of a single whisker. (b) Trial structure. A tone alerted mice to the time of possible stimulus onset. On Go trials, the whisker was stimulated with a sinusoidal deflection (0.5 s, 20 or 40 Hz). Mice responded by licking or not licking within a 1.8 s response window. (c) Four trial types are possible, based on the stimulus condition (present/absent) and the response (lick/no lick). (d) Behavioral detection performance varied with deflection speed for a single whisker (thin black lines) and three whiskers deflected simultaneously (thin purple lines). Plot symbols indicate different mice (n = 3). Thick lines show mean performance across mice for deflection of one (black) or three (purple) whiskers. Gray plot symbol at top-right shows performance (n = 2 mice) with strong multi-whisker stimulation. Gray bracket indicates range of speeds used for electrophysiology and imaging experiments. (e) Two-photon calcium imaging of primary somatosensory (S1) cortex during the tactile detection task. Left: cranial window showing region expressing the genetically encoded calcium indicator GCaMP6s. Right: example two-photon image over S1 showing hundreds of individual layer 2/3 neurons (white). (f) Example activity (ΔF/F0) traces from a single neuron for two Hit (blue), two Miss (black) and two Correct Rejection (red) trials. Inset: early portion of traces, before the earliest behavioral reaction times, used to calculate “evoked” ΔF/F0. (g) Cumulative histograms showing mean ΔF/F0 for Hit (blue), Miss (black) and Correct Rejection (red) trials for each neuron (n = 1,746 neurons from 6 mice).

Mentions: We trained mice in a simple head-fixed, Go/NoGo tactile detection task (Fig. 1a,b). Each trial began with an auditory cue to alert the mice to the time of possible stimulus onset (Fig. 1b). This cue was intended to eliminate ambiguity about the time at which the stimulus could arrive. A single whisker was deflected with a sinusoidal waveform (0.5 s, 20 or 40 Hz; Methods) on 50% of trials (Go trials). On the other 50% of trials, the whisker was not deflected. Lick responses occurring during a response window (Fig. 1b) determined trial outcome (Fig. 1c). Task performance varied with the strength (angular speed) of the whisker stimulus (Fig. 1d). Spiking responses increased monotonically for these whisker stimuli in the primary afferents, thalamus, and S1 (Supplementary Fig. 1a). When we randomly interleaved trials with stimulation of three whiskers rather than one whisker, performance increased even as the single-whisker curve began to saturate (Fig. 1d). Thus, tasks performed with a single whisker may be perceptually demanding for mice, even with relatively strong stimulation (cf. 19,22,23). Strong multi-whisker stimulation led to high performance (~85% correct), indicating that performance was limited by the stimulus rather than task engagement (Fig. 1d). For subsequent experiments, we used a stimulus strength (single whisker, ~500–900 degrees/s; cf. 24) that yielded a mixture of detection successes (Hits) and failures (Misses). Performance with this stimulus strength resulted in performance of ~70% correct even after several weeks of training (Supplementary Fig. 1d).We analyzed Hit, Miss and Correct Rejection trials (Fig. 1c), over periods prior to the typical reaction times (Supplementary Fig. 1). Because whisking produces self-generated tactile input that can affect detection behavior25, we limited analysis to periods of passive stimulation (Methods). Performance was abolished by reversibly silencing somatosensory cortex using optogenetic stimulation of GABAergic neurons19,22,23 (Supplementary Fig. 2).


Origins of choice-related activity in mouse somatosensory cortex.

Yang H, Kwon SE, Severson KS, O'Connor DH - Nat. Neurosci. (2015)

Choice-related activity in mouse primary somatosensory cortex(a) Tactile detection task based on deflections of a single whisker. (b) Trial structure. A tone alerted mice to the time of possible stimulus onset. On Go trials, the whisker was stimulated with a sinusoidal deflection (0.5 s, 20 or 40 Hz). Mice responded by licking or not licking within a 1.8 s response window. (c) Four trial types are possible, based on the stimulus condition (present/absent) and the response (lick/no lick). (d) Behavioral detection performance varied with deflection speed for a single whisker (thin black lines) and three whiskers deflected simultaneously (thin purple lines). Plot symbols indicate different mice (n = 3). Thick lines show mean performance across mice for deflection of one (black) or three (purple) whiskers. Gray plot symbol at top-right shows performance (n = 2 mice) with strong multi-whisker stimulation. Gray bracket indicates range of speeds used for electrophysiology and imaging experiments. (e) Two-photon calcium imaging of primary somatosensory (S1) cortex during the tactile detection task. Left: cranial window showing region expressing the genetically encoded calcium indicator GCaMP6s. Right: example two-photon image over S1 showing hundreds of individual layer 2/3 neurons (white). (f) Example activity (ΔF/F0) traces from a single neuron for two Hit (blue), two Miss (black) and two Correct Rejection (red) trials. Inset: early portion of traces, before the earliest behavioral reaction times, used to calculate “evoked” ΔF/F0. (g) Cumulative histograms showing mean ΔF/F0 for Hit (blue), Miss (black) and Correct Rejection (red) trials for each neuron (n = 1,746 neurons from 6 mice).
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Figure 1: Choice-related activity in mouse primary somatosensory cortex(a) Tactile detection task based on deflections of a single whisker. (b) Trial structure. A tone alerted mice to the time of possible stimulus onset. On Go trials, the whisker was stimulated with a sinusoidal deflection (0.5 s, 20 or 40 Hz). Mice responded by licking or not licking within a 1.8 s response window. (c) Four trial types are possible, based on the stimulus condition (present/absent) and the response (lick/no lick). (d) Behavioral detection performance varied with deflection speed for a single whisker (thin black lines) and three whiskers deflected simultaneously (thin purple lines). Plot symbols indicate different mice (n = 3). Thick lines show mean performance across mice for deflection of one (black) or three (purple) whiskers. Gray plot symbol at top-right shows performance (n = 2 mice) with strong multi-whisker stimulation. Gray bracket indicates range of speeds used for electrophysiology and imaging experiments. (e) Two-photon calcium imaging of primary somatosensory (S1) cortex during the tactile detection task. Left: cranial window showing region expressing the genetically encoded calcium indicator GCaMP6s. Right: example two-photon image over S1 showing hundreds of individual layer 2/3 neurons (white). (f) Example activity (ΔF/F0) traces from a single neuron for two Hit (blue), two Miss (black) and two Correct Rejection (red) trials. Inset: early portion of traces, before the earliest behavioral reaction times, used to calculate “evoked” ΔF/F0. (g) Cumulative histograms showing mean ΔF/F0 for Hit (blue), Miss (black) and Correct Rejection (red) trials for each neuron (n = 1,746 neurons from 6 mice).
Mentions: We trained mice in a simple head-fixed, Go/NoGo tactile detection task (Fig. 1a,b). Each trial began with an auditory cue to alert the mice to the time of possible stimulus onset (Fig. 1b). This cue was intended to eliminate ambiguity about the time at which the stimulus could arrive. A single whisker was deflected with a sinusoidal waveform (0.5 s, 20 or 40 Hz; Methods) on 50% of trials (Go trials). On the other 50% of trials, the whisker was not deflected. Lick responses occurring during a response window (Fig. 1b) determined trial outcome (Fig. 1c). Task performance varied with the strength (angular speed) of the whisker stimulus (Fig. 1d). Spiking responses increased monotonically for these whisker stimuli in the primary afferents, thalamus, and S1 (Supplementary Fig. 1a). When we randomly interleaved trials with stimulation of three whiskers rather than one whisker, performance increased even as the single-whisker curve began to saturate (Fig. 1d). Thus, tasks performed with a single whisker may be perceptually demanding for mice, even with relatively strong stimulation (cf. 19,22,23). Strong multi-whisker stimulation led to high performance (~85% correct), indicating that performance was limited by the stimulus rather than task engagement (Fig. 1d). For subsequent experiments, we used a stimulus strength (single whisker, ~500–900 degrees/s; cf. 24) that yielded a mixture of detection successes (Hits) and failures (Misses). Performance with this stimulus strength resulted in performance of ~70% correct even after several weeks of training (Supplementary Fig. 1d).We analyzed Hit, Miss and Correct Rejection trials (Fig. 1c), over periods prior to the typical reaction times (Supplementary Fig. 1). Because whisking produces self-generated tactile input that can affect detection behavior25, we limited analysis to periods of passive stimulation (Methods). Performance was abolished by reversibly silencing somatosensory cortex using optogenetic stimulation of GABAergic neurons19,22,23 (Supplementary Fig. 2).

Bottom Line: Spike trains from primary mechanoreceptive neurons did not predict choices about identical stimuli.An intracellular measure of stimulus sensitivity determined which neurons converted choice-related depolarization into spiking.Our results reveal how choice-related spiking emerges across neural circuits and within single neurons.

View Article: PubMed Central - PubMed

Affiliation: The Solomon H. Snyder Department of Neuroscience and Brain Science Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

ABSTRACT
During perceptual decisions about faint or ambiguous sensory stimuli, even identical stimuli can produce different choices. Spike trains from sensory cortex neurons can predict trial-to-trial variability in choice. Choice-related spiking is widely studied as a way to link cortical activity to perception, but its origins remain unclear. Using imaging and electrophysiology, we found that mouse primary somatosensory cortex neurons showed robust choice-related activity during a tactile detection task. Spike trains from primary mechanoreceptive neurons did not predict choices about identical stimuli. Spike trains from thalamic relay neurons showed highly transient, weak choice-related activity. Intracellular recordings in cortex revealed a prolonged choice-related depolarization in most neurons that was not accounted for by feed-forward thalamic input. Top-down axons projecting from secondary to primary somatosensory cortex signaled choice. An intracellular measure of stimulus sensitivity determined which neurons converted choice-related depolarization into spiking. Our results reveal how choice-related spiking emerges across neural circuits and within single neurons.

Show MeSH
Related in: MedlinePlus