Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations.

The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous. Here we use conditional genetics to chronically silence CA1 pyramidal cell transmission, ablating the ability of these neurons to recruit feedback inhibition in the local circuit, while recording physiological activity in mice. We find that this intervention leads to local pathophysiological events, with ripple amplitude and intrinsic frequency becoming significantly larger and spatially triggered local population spikes locked to the trough of the theta oscillation appearing during movement. These phenotypes demonstrate that feedback inhibition is crucial in maintaining local sparsity of activation and reveal the key role of lateral inhibition in CA1 in shaping circuit function.

Cortical sensory processing across motivational states during goal-directed behavior.

Behavioral states can influence performance of goal-directed sensorimotor tasks. Yet, it is unclear how altered neuronal sensory representations in these states relate to task performance and learning. We trained water-restricted mice in a two-whisker discrimination task to study cortical circuits underlying perceptual decision-making under different levels of thirst. We identified somatosensory cortices as well as the premotor cortex as part of the circuit necessary for task execution. Two-photon calcium imaging in these areas identified populations selective to sensory or motor events. Analysis of task performance during individual sessions revealed distinct behavioral states induced by decreasing levels of thirst-related motivation. Learning was better explained by improvements in motivational state control rather than sensorimotor association. Whisker sensory representations in the cortex were altered across behavioral states. In particular, whisker stimuli could be better decoded from neuronal activity during high task performance states, suggesting that state-dependent changes of sensory processing influence decision-making.

Learning-related congruent and incongruent changes of excitation and inhibition in distinct cortical areas.

Excitatory and inhibitory neurons in diverse cortical regions are likely to contribute differentially to the transformation of sensory information into goal-directed motor plans. Here, we investigate the relative changes across mouse sensorimotor cortex in the activity of putative excitatory and inhibitory neurons-categorized as regular spiking (RS) or fast spiking (FS) according to their action potential (AP) waveform-comparing before and after learning of a whisker detection task with delayed licking as perceptual report. Surprisingly, we found that the whisker-evoked activity of RS versus FS neurons changed in opposite directions after learning in primary and secondary whisker motor cortices, while it changed similarly in primary and secondary orofacial motor cortices. Our results suggest that changes in the balance of excitation and inhibition in local circuits concurrent with changes in the long-range synaptic inputs in distinct cortical regions might contribute to performance of delayed sensory-to-motor transformation.

Rapid suppression and sustained activation of distinct cortical regions for a delayed sensory-triggered motor response.

The neuronal mechanisms generating a delayed motor response initiated by a sensory cue remain elusive. Here, we tracked the precise sequence of cortical activity in mice transforming a brief whisker stimulus into delayed licking using wide-field calcium imaging, multiregion high-density electrophysiology, and time-resolved optogenetic manipulation. Rapid activity evoked by whisker deflection acquired two prominent features for task performance: (1) an enhanced excitation of secondary whisker motor cortex, suggesting its important role connecting whisker sensory processing to lick motor planning; and (2) a transient reduction of activity in orofacial sensorimotor cortex, which contributed to suppressing premature licking. Subsequent widespread cortical activity during the delay period largely correlated with anticipatory movements, but when these were accounted for, a focal sustained activity remained in frontal cortex, which was causally essential for licking in the response period. Our results demonstrate key cortical nodes for motor plan generation and timely execution in delayed goal-directed licking.

Axonal and Dendritic Morphology of Excitatory Neurons in Layer 2/3 Mouse Barrel Cortex Imaged Through Whole-Brain Two-Photon Tomography and Registered to a Digital Brain Atlas.

Communication between cortical areas contributes importantly to sensory perception and cognition. On the millisecond time scale, information is signaled from one brain area to another by action potentials propagating across long-range axonal arborizations. Here, we develop and test methodology for imaging and annotating the brain-wide axonal arborizations of individual excitatory layer 2/3 neurons in mouse barrel cortex through single-cell electroporation and two-photon serial section tomography followed by registration to a digital brain atlas. Each neuron had an extensive local axon within the barrel cortex. In addition, individual neurons innervated subsets of secondary somatosensory cortex; primary somatosensory cortex for upper limb, trunk, and lower limb; primary and secondary motor cortex; visual and auditory cortical regions; dorsolateral striatum; and various fiber bundles. In the future, it will be important to assess if the diversity of axonal projections across individual layer 2/3 mouse barrel cortex neurons is accompanied by functional differences in their activity patterns.

Cortical circuits for transforming whisker sensation into goal-directed licking.

Animals can learn to use sensory stimuli to generate motor actions in order to obtain rewards. However, the precise neuronal circuits driving learning and execution of a specific goal-directed sensory-to-motor transformation remain to be elucidated. Here, we review progress in understanding the contribution of cortical neuronal circuits to a task in which head-restrained water-restricted mice learn to lick a reward spout in response to whisker deflection. We first examine 'innate' pathways for whisker sensory processing and licking motor control, and then discuss how these might become linked through reward-based learning, perhaps enabled by cholinergic-gated and dopaminergic-gated plasticity. The aim is to uncover the synaptically connected neuronal pathways that mediate reward-based learning and execution of a well-defined sensory-to-motor transformation.

Anatomically and functionally distinct thalamocortical inputs to primary and secondary mouse whisker somatosensory cortices.

Subdivisions of mouse whisker somatosensory thalamus project to cortex in a region-specific and layer-specific manner. However, a clear anatomical dissection of these pathways and their functional properties during whisker sensation is lacking. Here, we use anterograde trans-synaptic viral vectors to identify three specific thalamic subpopulations based on their connectivity with brainstem. The principal trigeminal nucleus innervates ventral posterior medial thalamus, which conveys whisker-selective tactile information to layer 4 primary somatosensory cortex that is highly sensitive to self-initiated movements. The spinal trigeminal nucleus innervates a rostral part of the posterior medial (POm) thalamus, signaling whisker-selective sensory information, as well as decision-related information during a goal-directed behavior, to layer 4 secondary somatosensory cortex. A caudal part of the POm, which apparently does not receive brainstem input, innervates layer 1 and 5A, responding with little whisker selectivity, but showing decision-related modulation. Our results suggest the existence of complementary segregated information streams to somatosensory cortices.

Distinct Contributions of Whisker Sensory Cortex and Tongue-Jaw Motor Cortex in a Goal-Directed Sensorimotor Transformation.

The neural circuits underlying goal-directed sensorimotor transformations in the mammalian brain are incompletely understood. Here, we compared the role of primary tongue-jaw motor cortex (tjM1) and primary whisker sensory cortex (wS1) in head-restrained mice trained to lick a reward spout in response to whisker deflection. Two-photon microscopy combined with microprisms allowed imaging of neuronal network activity across cortical layers in transgenic mice expressing a genetically encoded calcium indicator. Early-phase activity in wS1 encoded the whisker sensory stimulus and was necessary for detection of whisker stimuli. Activity in tjM1 encoded licking direction during task execution and was necessary for contralateral licking. Pre-stimulus activity in tjM1, but not wS1, was predictive of lick direction and contributed causally to small preparatory jaw movements. Our data reveal a shift in coding scheme from wS1 to tjM1, consistent with the hypothesis that these areas represent cortical start and end points for this goal-directed sensorimotor transformation.

Continuous wavelet application for the assessment of neural potential interaction during time discrimination task.

The aim of the paper is to assess the interaction of the neural potentials during a time discrimination psychoacoustic task. Ten subjects participated in the experiment and were asked about the equality of two acoustic pulses: one reference of 500ms and one trial that varied from 420ms to 620ms. During the experimental procedure, Electroencephalogram (EEG) and Event Related Potential (ERP) signals were recorded. The analysis combines results from Continuous Wavelet signal processing and subjects responses which were analyzed based on psychoacoustic theory. The Wavelet Coherence metric index is employed to assess the interaction of neural potentials. The results indicate the points at which the duration of the trial pulse is equal to 560ms and 460ms as the minimum and maximum of the Wavelet Coherence metric index, respectively. This observation is valid in most electrodes, for all basic EEG rhythms, revealing in parallel the differentiation of the gamma rhythm, in relation to the others. These maximum and minimum values are correlated to the Just Noticeable Difference (JND) in pulses duration, calculated by the psychoacoustic analysis.