Rapid, learning-induced inhibitory synaptogenesis in murine barrel field

The structure of neurons changes during development and in response to injury or alteration in sensory experience. Changes occur in the number, shape, and dimensions of dendritic spines together with their synapses. However, precise data on these changes in response to learning are sparse. Here, we show using quantitative transmission electron microscopy that a simple form of learning involving mystacial vibrissae results in approximately 70% increase in the density of inhibitory synapses on spines of neurons located in layer IV barrels that represent the stimulated vibrissae. The spines contain one asymmetrical (excitatory) and one symmetrical (inhibitory) synapse (double-synapse spines), and their density increases threefold as a result of learning with no apparent change in the density of asymmetrical synapses. This effect seems to be specific for learning because pseudoconditioning (in which the conditioned and unconditioned stimuli are delivered at random) does not lead to the enhancement of symmetrical synapses but instead results in an upregulation of asymmetrical synapses on spines. Symmetrical synapses of cells located in barrels receiving the conditioned stimulus also show a greater concentration of GABA in their presynaptic terminals. These results indicate that the immediate effect of classical conditioning in the "conditioned" barrels is rapid, pronounced, and inhibitory

Psychometric Curve and Behavioral Strategies for Whisker-Based Texture Discrimination in Rats

The rodent whisker system is a major model for understanding neural mechanisms for tactile sensation of surface texture (roughness). Rats discriminate surface texture using the whiskers, and several theories exist for how texture information is physically sensed by the long, moveable macrovibrissae and encoded in spiking of neurons in somatosensory cortex. However, evaluating these theories requires a psychometric curve for texture discrimination, which is lacking. Here we trained rats to discriminate rough vs. fine sandpapers and grooved vs. smooth surfaces. Rats intermixed trials at macrovibrissa contact distance (nose >2 mm from surface) with trials at shorter distance (nose <2 mm from surface). Macrovibrissae were required for distant contact trials, while microvibrissae and non-whisker tactile cues were used for short distance trials. A psychometric curve was measured for macrovibrissa-based sandpaper texture discrimination. Rats discriminated rough P150 from smoother P180, P280, and P400 sandpaper (100, 82, 52, and 35 µm mean grit size, respectively). Use of olfactory, visual, and auditory cues was ruled out. This is the highest reported resolution for rodent texture discrimination, and constrains models of neural coding of texture information

Do Gravity-Related Sensory Information Enable the Enhancement of Cortical Proprioceptive Inputs When Planning a Step in Microgravity?

International audienceWe recently found that the cortical response to proprioceptive stimulation was greater when participants were planning a step than when they stood still, and that this sensory facilitation was suppressed in microgravity. The aim of the present study was to test whether the absence of gravity-related sensory afferents during movement planning in microgravity prevented the proprioceptive cortical processing to be enhanced. We reestablished a reference frame in microgravity by providing and translating a horizontal support on which the participants were standing and verified whether this procedure restored the proprioceptive facilitation. The slight translation of the base of support (lateral direction), which occurred prior to step initiation, stimulated at least cutaneous and vestibular receptors. The sensitivity to proprioceptive stimulation was assessed by measuring the amplitude of the cortical somatosensory-evoked potential (SEP, over the Cz electrode) following the vibration of the leg muscle. The vibration lasted 1 s and the participants were asked to either initiate a step at the vibration offset or to remain still. We found that the early SEP (90–160 ms) was smaller when the platform was translated than when it remained stationary, revealing the existence of an interference phenomenon (i.e., when proprioceptive stimulation is preceded by the stimulation of different sensory modalities evoked by the platform translation). By contrast, the late SEP (550 ms post proprioceptive stimulation onset) was greater when the translation preceded the vibration compared to a condition without pre-stimulation (i.e., no translation). This suggests that restoring a body reference system which is impaired in microgravity allowed a greater proprioceptive cortical processing. Importantly, however, the late SEP was similarly increased when participants either produced a step or remained still. We propose that the absence of step-induced facilitation of proprioceptive cortical processing results from a decreased weight of proprioception in the absence of balance constraints in microgravity

Novel two-alternative forced choice paradigm for bilateral vibrotactile whisker frequency discrimination in head-fixed mice and rats

Rats and mice receive a constant bilateral stream of tactile information with their large mystacial vibrissae when navigating in their environment. In a two-alternative forced choice paradigm (2-AFC), head-fixed rats and mice learned to discriminate vibrotactile frequencies applied simultaneously to individual whiskers on the left and right sides of the snout. Mice and rats discriminated 90-Hz pulsatile stimuli from pulsatile stimuli with lower repetition frequencies (10-80 Hz) but with identical kinematic properties in each pulse. Psychometric curves displayed an average perceptual threshold of 50.6-Hz and 53.0-Hz frequency difference corresponding to Weber fractions of 0.56 and 0.58 in mice and rats, respectively. Both species performed >400 trials a day (>200 trials per session, 2 sessions/day), with a peak performance of >90% correct responses. In general, rats and mice trained in the identical task showed comparable psychometric curves. Behavioral readouts, such as reaction times, learning rates, trial omissions, and impulsivity, were also very similar in the two species. Furthermore, whisking of the animals before stimulus presentation reduced task performance. This behavioral paradigm, combined with whisker position tracking, allows precise stimulus control in the 2-AFC task for head-fixed rodents. It is compatible with state-of-the-art neurophysiological recording techniques, such as electrophysiology and two-photon imaging, and therefore represents a valuable framework for neurophysiological investigations of perceptual decision-making

Two-point tactile discrimination ability is influenced by temporal features of stimulation

Two-point discrimination threshold is commonly used for assessing tactile spatial resolution. Since the effect of temporal features of cutaneous test stimulation on spatial discrimination ability is not yet well known, we determined whether the ability to discriminate between two stimulus locations varies with the interstimulus interval (ISI) of sequentially presented tactile stimuli or the length of the stimulus train. Electrotactile stimuli were applied to one or two locations on the skin of the thenar eminence of the hand in healthy human subjects. Tactile discrimination ability was determined using methods based on the signal detection theory allowing the assessment of sensory performance, independent of the subject's response criterion. With stimulus pairs, the ability to discriminate spatial features of stimulation (one location vs. two stimulus locations 4 cm apart) was improved when the ISI was equal to or longer than that required for tactile temporal discrimination. With stimulus trains, the ability to discriminate spatial features of stimulation was significantly improved with an increase in the stimulus train (from 3 to 11 pulses corresponding to train lengths from 40 to 200 ms). These results indicate that temporal features of tactile stimulation significantly influence sensory performance in a tactile spatial discrimination task. Precise control of temporal stimulus parameters should help to reduce variations in results on the two-point discrimination threshold

Developmental origins of cortical hyperexcitability in Huntington's disease: Review and new observations

Huntington's disease (HD), an inherited neurodegenerative disorder that principally affects striatum and cerebral cortex, is generally thought to have an adult onset. However, a small percentage of cases develop symptoms before 20&nbsp;years of age. This juvenile variant suggests that brain development may be altered in HD. Indeed, recent evidence supports an important role of normal huntingtin during embryonic brain development and mutations in this protein cause cortical abnormalities. Functional studies also demonstrated that the cerebral cortex becomes hyperexcitable with disease progression. In this review, we examine clinical and experimental evidence that cortical development is altered in HD. We also provide preliminary evidence that cortical pyramidal neurons from R6/2 mice, a model of juvenile HD, are hyperexcitable and display dysmorphic processes as early as postnatal day 7. Further, some symptomatic mice present with anatomical abnormalities reminiscent of human focal cortical dysplasia, which could explain the occurrence of epileptic seizures in this genetic mouse model and in children with juvenile HD. Finally, we discuss recent treatments aimed at correcting abnormal brain development