Mapping specific sensory features to future motor actions is a crucial capability of mammalian nervous systems. We investigated the role of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice during performance of a memory-guided visual discrimination task. Large-scale calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous responses spanning all task epochs (stimulus, delay, response). Population analyses demonstrated unique encoding of stimulus identity and behavioral choice information across regions, with V1 encoding stimulus, fMC encoding choice even early in the trial, and PPC multiplexing the two variables. Optogenetic inhibition during behavior revealed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus identity can thus be rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution.DOI: http://dx.doi.org/10.7554/eLife.13764.001

The posterior parietal cortex (PPC) has been implicated in perceptual decisions, but whether its role is specific to sensory processing or sensorimotor transformation is not well understood. Here, we trained mice to perform a go/no-go visual discrimination task and imaged the activity of neurons in primary visual cortex (V1) and PPC during engaged behavior and passive viewing. Unlike V1 neurons, which respond robustly to stimuli in both conditions, most PPC neurons respond exclusively during task engagement. To test whether signals in PPC primarily encoded the stimulus or the animal’s impending choice, we image the same neurons before and after re-training mice with a reversed sensorimotor contingency. Unlike V1 neurons, most PPC neurons reflect the animal’s choice of the new target stimulus after re-training. Mouse PPC is therefore strongly task-dependent, reflects choice more than stimulus, and may play a role in the transformation of visual inputs into motor commands.

SUMMARY Purpose To investigate the effects of low frequency stimulation (LFS) of a fiber track for the suppression of spontaneous seizures described by Nissinen in a rat model of human temporal lobe epilepsy. Methods Stimulation electrodes were implanted into the ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model of human temporal lobe epilepsy (n = 7). Two recordings electrodes were placed in the CA3 regions bilaterally and neural data was recorded for a minimum of six weeks. LFS (60 minute train of 1Hz biphasic square wave pulses, each 0.1ms in duration and 200μA in amplitude, followed by 15 minutes of rest) was applied to the VHC for, two weeks, 24 hours a day. Key Findings The baseline mean seizure frequency of the study animals was 3.7 seizures per day. The seizures were significantly reduced by the application of LFS in every animal (n=7). By the end of the two-week period of stimulation, there was a significant 90% (<1 seizure/day) reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period following LFS (p < 0.05) when compared to baseline. LFS also resulted in a significant reduction of hippocampal interictal spike frequency (71%, p < 0.05), during two weeks LFS session. The hippocampal histological analysis showed no significant difference between rats that received LFS and SE-induction and those that had only received SE-induction. None of the animals showed any symptomatic hemorrhage, infection or complication. Significance LFS applied at a frequency of 1Hz significantly reduced both the excitability of the neural tissue as well as the seizure frequency in a rat model of human temporal lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be an effective method for the suppression of spontaneous seizures in a temporal lobe model of epilepsy in rats and could be lead to the development of the new therapeutic modality for human patients with temporal lobe epilepsy.

Sensorimotor behaviors require processing of behaviorally relevant sensory cues and the ability to select appropriate responses from a vast behavioral repertoire. Modulation by the prefrontal cortex (PFC) is thought to be key for both processes, but the precise role of specific circuits remains unclear. We examined the sensorimotor function of anatomically distinct outputs from a subdivision of the mouse PFC, the anterior cingulate cortex (ACC). Using a visually guided two-choice behavioral paradigm with multiple cue-response mappings, we dissociated the sensory and motor response components of sensorimotor control. Projection-specific two-photon calcium imaging and optogenetic manipulations show that ACC outputs to the superior colliculus, a key midbrain structure for response selection, principally coordinate specific motor responses. Importantly, ACC outputs exert control by reducing the innate response bias of the superior colliculus. In contrast, ACC outputs to the visual cortex facilitate sensory processing of visual cues. Our results ascribe motor and sensory roles to ACC projections to the superior colliculus and the visual cortex and demonstrate for the first time a circuit motif for PFC function wherein anatomically non-overlapping output pathways coordinate complementary but distinct aspects of visual sensorimotor behavior.

The posterior parietal cortex (PPC) has been implicated in perceptual decisions, but whether its role is specific to sensory processing or sensorimotor transformation is not well understood. To distinguish these possibilities, we trained mice of either sex to perform a visual discrimination task and imaged the activity of PPC populations during both engaged behavior and passive viewing. Unlike neurons in primary visual cortex (V1), which responded robustly to stimuli in both conditions, most neurons in PPC responded exclusively during task engagement. However, PPC responses were heterogeneous, with a smaller subset of neurons exhibiting stimulus-driven, contrast-dependent responses in both conditions. Neurons in PPC also exhibit stronger modulation by noise correlations relative to V1, as illustrated by a generalized linear model that takes into account both task variables and between-neuron correlations. To test whether PPC responses primarily encoded the stimulus or the learned sensorimotor contingency, we imaged the same neurons before and after re-training mice on a reversed task contingency. Unlike V1 neurons, most PPC neurons exhibited a dramatic shift in selectivity after re-training and reflected the new sensorimotor contingency, while a smaller subset of neurons preserved their stimulus selectivity. Mouse PPC is therefore strongly task-dependent, contains heterogeneous populations sensitive to stimulus and choice, and may play an important role in the flexible transformation of sensory inputs into motor commands.Significance StatementPerceptual decision making involves both processing of sensory information and mapping that information onto appropriate motor commands via learned sensorimotor associations. While visual cortex (V1) is known to be critical for sensory processing, it is unclear what circuits are involved in the process of sensorimotor transformation. While the mouse posterior parietal cortex (PPC) has been implicated in visual decisions, its specific role has been controversial. By imaging population activity while manipulating task engagement and sensorimotor contingencies, we demonstrate that PPC, unlike V1, is highly task-dependent, heterogeneous, and sensitive to the learned task demands. Our results suggest that PPC is more than a visual area, and may instead be involved in the flexible mapping of visual information onto appropriate motor actions.

Ray Guillery made major contributions to our understanding of the development and function of the brain. One of his principal conceptual insights, developed together with Murray Sherman [S.M. Sherman & R.W. Guillery (2001) Exploring the Thalamus. Elsevier, Amstrerdam; S. Sherman & R. Guillery (2006) Exploring the Thalamus and Its Role in Cortical Functioning. Academic Press, New York, NY; S.M. Sherman & R.W. Guillery (2013) Functional Connections of Cortical Areas: A New View from the Thalamus. MIT Press, Cambridge, MA and then in his last book (R. Guillery (2017) The Brain as a Tool: A Neuroscientist's Account. Oxford University Press, Oxford, UK)], was that the brain is a 'tool' to understand the world. In this view, the brain does not passively process sensory information and use the result to inform motor outputs. Rather, sensory and motor signals are widely broadcast and inextricably linked, with ongoing sensorimotor transformations serving as the basis for interaction with the outside world. Here, we describe recent studies from our laboratory and others which demonstrate this astute framing of the link among sensation, perception, and action postulated by Guillery and others [G. Deco & E.T. Rolls (2005) Prog Neurobiol, 76, 236-256; P. Cisek & J.F. Kalaska (2010) Annu Rev Neurosci, 33, 269-298]. Guillery situated his understanding in the deeply intertwined relationship between the thalamus and cortex, and importantly in the feedback from cortex to thalamus which in turn influences feed-forward drive to cortex [S.M. Sherman & R.W. Guillery (2001) Exploring the Thalamus. Elsevier, Amstrerdam; S. Sherman & R. Guillery (2006) Exploring the Thalamus and Its Role in Cortical Functioning. Academic Press, New York, NY]. We extend these observations to argue that brain mechanisms for sensorimotor transformations involve cortical and subcortical circuits that create internal models as a substrate for action, that a key role of sensory inputs is to update such models, and that a major function of sensorimotor processing underlying cognition is to enable action selection and execution.

SummaryThe immense behavioral repertoire of animals necessitates mechanisms that select and suppress 15 specific actions depending on current goals. The prefrontal cortex (PFC) has been suggested to orchestrate these processes by biasing activity in its target structures, but how its vastly converging inputs and diverging outputs are coordinated to control goal-oriented actions remains unclear. Here we use a bilateral task in which mice select between symmetric but opposing actions to show that distinct outputs from a subdivision of the PFC, the anterior cingulate cortex (ACC), promote 20 correct and suppress incorrect actions. Surprisingly, ACC outputs to the superior colliculus principally inhibit incorrect actions. Optogenetic analyses and a projection-based activity model make the unexpected prediction that feedback from the ACC to the visual cortex promotes correct actions, which we confirm. Our results show that anatomically non-overlapping but functionally complementary PFC outputs bidirectionally control actions, and suggest a candidate organizing 25 principle for PFC circuits.

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