Correction: Data-driven analyses of motor impairments in animal models of neurological disorders.

[This corrects the article DOI: 10.1371/journal.pbio.3000516.].

Sensory experience selectively reorganizes the late component of evoked responses.

In response to sensory stimulation, the cortex exhibits an early transient response followed by late and slower activation. Recent studies suggest that the early component represents features of the stimulus while the late component is associated with stimulus perception. Although very informative, these studies only focus on the amplitude of the evoked responses to study its relationship with sensory perception. In this work, we expand upon the study of how patterns of evoked and spontaneous activity are modified by experience at the mesoscale level using voltage and extracellular glutamate transient recordings over widespread regions of mouse dorsal neocortex. We find that repeated tactile or auditory stimulation selectively modifies the spatiotemporal patterns of cortical activity, mainly of the late evoked response in anesthetized mice injected with amphetamine and also in awake mice. This modification lasted up to 60 min and results in an increase in the amplitude of the late response after repeated stimulation and in an increase in the similarity between the spatiotemporal patterns of the late early evoked response. This similarity increase occurs only for the evoked responses of the sensory modality that received the repeated stimulation. Thus, this selective long-lasting spatiotemporal modification of the cortical activity patterns might provide evidence that evoked responses are a cortex-wide phenomenon. This work opens new questions about how perception-related cortical activity changes with sensory experience across the cortex.

Formation and reverberation of sequential neural activity patterns evoked by sensory stimulation are enhanced during cortical desynchronization.

Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.

In vivo BDNF modulation of hippocampal mossy fiber plasticity induced by high frequency stimulation.

Changes in synaptic efficacy and morphology have been proposed as mechanisms underlying learning and memory processes. In our previous studies, high frequency stimulation (HFS) sufficient to induce LTP at the hippocampal mossy fiber (MF) pathway, leads to MF synaptogenesis, in a prominent contralateral form, at the stratum oriens of hippocampal CA3 area. Recently we reported that acute intrahippocampal microinfusion of BDNF induces a lasting potentiation of synaptic efficacy at the MF projection accompanied by a structural reorganization at the CA3 area within the stratum oriens region in a prominent ipsilateral form. It is considered that the capacity of synapses to express plastic changes is itself subject to variation dependent on previous experience. Here we used intrahippocampal microinfusion of BDNF to analyze its effects on functional and structural synaptic plasticity induced by subsequent mossy fiber HFS sufficient to induce LTP in adult rats, in vivo. Our results show that BDNF modifies the ability of the MF pathway to present LTP by HFS. Moreover BDNF modified the structural reorganization pattern produced by HFS, presenting a balanced bilateral appearance. Microinfusion of K252a blocks the functional and morphological effects produced by BDNF, revealing that the BDNF modulation is dependent on its TrkB receptor activation. These findings support the idea that BDNF actions modify subsequent synaptic plasticity; a homeostatic mechanism thought to be essential for synaptic integration among prolonged temporal domains in the adult mammalian brain.

Recording large-scale neuronal ensembles with silicon probes in the anesthetized rat.

Large scale electrophysiological recordings from neuronal ensembles offer the opportunity to investigate how the brain orchestrates the wide variety of behaviors from the spiking activity of its neurons. One of the most effective methods to monitor spiking activity from a large number of neurons in multiple local neuronal circuits simultaneously is by using silicon electrode arrays. Action potentials produce large transmembrane voltage changes in the vicinity of cell somata. These output signals can be measured by placing a conductor in close proximity of a neuron. If there are many active (spiking) neurons in the vicinity of the tip, the electrode records combined signal from all of them, where contribution of a single neuron is weighted by its 'electrical distance'. Silicon probes are ideal recording electrodes to monitor multiple neurons because of a large number of recording sites (+64) and a small volume. Furthermore, multiple sites can be arranged over a distance of millimeters, thus allowing for the simultaneous recordings of neuronal activity in the various cortical layers or in multiple cortical columns (Fig. 1). Importantly, the geometrically precise distribution of the recording sites also allows for the determination of the spatial relationship of the isolated single neurons. Here, we describe an acute, large-scale neuronal recording from the left and right forelimb somatosensory cortex simultaneously in an anesthetized rat with silicon probes (Fig. 2).