Experience-Dependent Development and Maintenance of Binocular Neurons in the Mouse Visual Cortex

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A Direct Projection from Mouse Primary Visual Cortex to Dorsomedial Striatum

The mammalian striatum receives inputs from many cortical areas, but the existence of a direct axonal projection from the primary visual cortex (V1) is controversial. In this study we use anterograde and retrograde tracing techniques to demonstrate that V1 directly innervates a topographically defined longitudinal strip of dorsomedial striatum in mice. We find that this projection forms functional excitatory synapses with direct and indirect pathway striatal projection neurons (SPNs) and engages feed-forward inhibition onto these cells. Importantly, stimulation of V1 afferents is sufficient to evoke phasic firing in SPNs. These findings therefore identify a striatal region that is functionally innervated by V1 and suggest that early visual processing may play an important role in striatal-based behaviors.     

成年大鼠体感皮层局限损伤引起的代表区重组

本文目的是探讨在成年大鼠初级体感皮层（ＳＩ）内进行局限损毁能否引起损毁区周围的代表区重组。在氯胺酮麻醉下用微电极技术测定隐神经代表区（ＳＡＲ）和坐骨神经代表区（ＳＣＲ）,然后用铂电极对ＳＡＲ进行选择性电解损毁。三至四周后进行重复测定。结果表明,在１４例所观察的大鼠中,９例在原损毁区以外发现新生的ＳＡＲ,其面积为０．２０±０．０８ｍｍ２。这表明成年大鼠ＳＩ神经元在中枢损伤后具有一定的重组能力。     

Cortico-Cortical Interactions Influence Binocularity of the Primary Visual Cortex of Adult Mice

Electrophysiological studies have revealed that a large proportion of the mouse primary visual cortex (V1) receives input also from the ipsilateral eye. This is surprising as most optic nerve fibers cross at the optic chiasm in mice. Inactivating V1 of one hemisphere has recently demonstrated a strong contribution of one hemisphere''s activity on binocularity of single units and visually evoked potentials of V1 in the other hemisphere of young rats and of single units in young adult mice. Here we used intrinsic signal optical imaging to quantitatively study the influence of cortico-cortical connections on the magnitude of neuronal activation in the entire binocular zone of adult mouse V1. We simultaneously measured V1-activity of both hemispheres in adult C57BL/6J mice before and after blocking sensory-driven activity in one hemisphere with muscimol. In V1 contralateral to the inactivation, ipsilateral eye evoked activity was reduced by on average 18% while contralateral eye evoked activity did not change. Our results clearly show that cortico-cortical interactions exert a global amplification of ipsilateral eye evoked activity in adult mouse V1.     

Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation Reflecting Use-Dependent Plasticity

Previous research suggests that anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) modulates NMDA receptor dependent processes that mediate synaptic plasticity. Here we test this proposal by applying anodal versus sham tDCS while subjects practiced to flex the thumb as fast as possible (ballistic movements). Repetitive practice of this task has been shown to result in performance improvements that reflect use-dependent plasticity resulting from NMDA receptor mediated, long-term potentiation (LTP)-like processes. Using a double-blind within-subject cross-over design, subjects (n=14) participated either in an anodal or a sham tDCS session which were at least 3 months apart. Sham or anodal tDCS (1 mA) was applied for 20 min during motor practice and retention was tested 30 min, 24 hours and one week later. All subjects improved performance during each of the two sessions (p < 0.001) and learning gains were similar. Our main result is that long term retention performance (i.e. 1 week after practice) was significantly better when practice was performed with anodal tDCS than with sham tDCS (p < 0.001). This effect was large (Cohen’s d=1.01) and all but one subject followed the group trend. Our data strongly suggest that anodal tDCS facilitates long-term memory formation reflecting use-dependent plasticity. Our results support the notion that anodal tDCS facilitates synaptic plasticity mediated by an LTP-like mechanism, which is in accordance with previous research.     

A Postnatal Critical Period for Orientation Plasticity in the Cat Visual Cortex

Orientation selectivity of primary visual cortical neurons is an important requisite for shape perception. Although numerous studies have been previously devoted to a question of how orientation selectivity is established and elaborated in early life, how the susceptibility of orientation plasticity to visual experience changes in time remains unclear. In the present study, we showed a postnatal sensitive period profile for the modifiability of orientation selectivity in the visual cortex of kittens reared with head-mounted goggles for stable single-orientation exposure. When goggle rearing (GR) started at P16-P30, 2 weeks of GR induced a marked over-representation of the exposed orientation, and 2 more weeks of GR consolidated the altered orientation maps. GR that started later than P50, in turn, induced the under-representation of the exposed orientation. Orientation plasticity in the most sensitive period was markedly suppressed by cortical infusion of NMDAR antagonist. The present study reveals that the plasticity and consolidation of orientation selectivity in an early life are dynamically regulated in an experience-dependent manner.     

Spike Timing-Dependent Synaptic Plasticity in Visual Cortex: A Modeling Study

Recent studies show that synaptic modification depends critically on the relative spike timing of pre- and postsynaptic neurons. Here we explore the functional implications of spike timing-dependent synaptic plasticity in the visual cortex using a model circuit with modifiable intracortical excitatory connections. First we simulated the experiments using two-point stimuli, in which two visual stimuli in a topographically represented feature space were repeatedly presented in quick succession, and found that tuning of the cortical neurons was modified in a manner similar to that observed experimentally. We then explored the dependence of results on the model parameter and identified the intracortical parameters that were critical for the magnitude of the shifts and obtained a simple relationship between the amount of shift and (S = (_EXTC^rec_exc)/_INHC^rec_inh). Finally we investigated the effects of moving stimuli in a topographically represented visual space and found that they can effectively induce spike timing-dependent modification of the intracortical connections. It suggests the importance of moving stimuli in dynamic modification of the cortical maps through spike timing-dependent synaptic plasticity.     

Adult Plasticity in the Subcortical Auditory Pathway of the Maternal Mouse

Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system – motherhood – is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.     

Post-Stroke Longitudinal Alterations of Inter-Hemispheric Correlation and Hemispheric Dominance in Mouse Pre-Motor Cortex

Purpose

Limited restoration of function is known to occur spontaneously after an ischemic injury to the primary motor cortex. Evidence suggests that Pre-Motor Areas (PMAs) may “take over” control of the disrupted functions. However, little is known about functional reorganizations in PMAs. Forelimb movements in mice can be driven by two cortical regions, Caudal and Rostral Forelimb Areas (CFA and RFA), generally accepted as primary motor and pre-motor cortex, respectively. Here, we examined longitudinal changes in functional coupling between the two RFAs following unilateral photothrombotic stroke in CFA (mm from Bregma: +0.5 anterior, +1.25 lateral).

Methods

Local field potentials (LFPs) were recorded from the RFAs of both hemispheres in freely moving injured and naïve mice. Neural signals were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke animals) through one bipolar electrode per hemisphere placed in the center of RFA, with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of artifact removal and analysed through: spectral,cross-correlation, mutual information and Granger causality analysis.

Results

Spectral analysis demonstrated an early decrease (day 9) in the alpha band power in both the RFAs. In the late sub-acute period (days 16 and 23), inter-hemispheric functional coupling was reduced in ischemic animals, as shown by a decrease in the cross-correlation and mutual information measures. Within the gamma and delta bands, correlation measures were already reduced at day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less balanced activity in the two RFAs after stroke, with more frequent oscillations of hemispheric dominance.

Conclusions

These results indicate robust electrophysiological changes in PMAs after stroke. Specifically, we found alterations in transcallosal connectivity, with reduced inter-hemispheric functional coupling and a fluctuating dominance pattern. These reorganizations may underlie vicariation of lost functions following stroke.     

Dopamine in Motor Cortex Is Necessary for Skill Learning and Synaptic Plasticity

Preliminary evidence indicates that dopamine given by mouth facilitates the learning of motor skills and improves the recovery of movement after stroke. The mechanism of these phenomena is unknown. Here, we describe a mechanism by demonstrating in rat that dopaminergic terminals and receptors in primary motor cortex (M1) enable motor skill learning and enhance M1 synaptic plasticity. Elimination of dopaminergic terminals in M1 specifically impaired motor skill acquisition, which was restored upon DA substitution. Execution of a previously acquired skill was unaffected. Reversible blockade of M1 D1 and D2 receptors temporarily impaired skill acquisition but not execution, and reduced long-term potentiation (LTP) within M1, a form of synaptic plasticity critically involved in skill learning. These findings identify a behavioral and functional role of dopaminergic signaling in M1. DA in M1 optimizes the learning of a novel motor skill.