Initial neighborhood biases and the quality of motion stimulation jointly influence the rapid emergence of direction preference in visual cortex.

Visual experience plays a critical role in the development of direction-selective responses in ferret visual cortex. In visually naive animals, presentation of a bidirectional "training" stimulus induces rapid increases in the direction-selective responses of single neurons that can be predicted by small but significant direction biases that are present in neighboring neurons at the onset of stimulation. In this study we used in vivo two-photon imaging of calcium signals to further explore the contribution of visual experience to the emergence of direction- selective responses in ferret visual cortex. The first set of experiments was designed to determine whether visual experience is required for the development of the initial neighborhood bias. In animals that were dark-reared until the time of eye opening, we found that individual neurons exhibited weak direction-selective responses accompanied by a reduced but statistically significant neighborhood bias, indicating that both features arise without the need for visual experience. The second set of experiments used a unidirectional training stimulus to assess the relative roles of the neighborhood bias and visual experience in determining the direction preference that cortical neurons acquire during direction training. We found that neurons became more responsive to the trained direction even when they were located in regions of the cortex with an initial neighborhood bias for the direction opposite the training stimulus. Together, these results suggest an adaptive developmental strategy for the elaboration of direction-selective responses, one in which experience-independent mechanisms provide a symmetry-breaking seed for the instructive effects of visual experience.

A unifying model for timing of walking onset in humans and other mammals.

The onset of walking is a fundamental milestone in motor development of humans and other mammals, yet little is known about what factors determine its timing. Hoofed animals start walking within hours after birth, rodents and small carnivores require days or weeks, and nonhuman primates take months and humans approximately a year to achieve this locomotor skill. Here we show that a key to the explanation for these differences is that time to the onset of walking counts from conception and not from birth, indicating that mechanisms underlying motor development constitute a functional continuum from pre- to postnatal life. In a multiple-regression model encompassing 24 species representative of 11 extant orders of placental mammals that habitually walk on the ground, including humans, adult brain mass accounted for 94% of variance in time to walking onset postconception. A dichotomous variable reflecting species differences in functional limb anatomy accounted for another 3.8% of variance. The model predicted the timing of walking onset in humans with high accuracy, showing that this milestone in human motor development occurs no later than expected given the mass of the adult human brain, which in turn reflects the duration of its ontogenetic development. The timing of motor development appears to be highly conserved in mammalian evolution as the ancestors of some of the species in the sample presented here diverged in phylogenesis as long as 100 million years ago. Fundamental patterns of early human life history may therefore have evolved before the evolution of primates.

Spontaneous movements: Effect of denervation and relation to the adaptation of nociceptive withdrawal reflexes in the rat.

Spontaneous movements are a ubiquitous phenomenon during development. Recently, we demonstrated that these movements play a key role in the functional adaptation of spinal reflex circuits. Here, we analyse the role of afferent input in the generation of spontaneous movements and characterize the occurrence of different types of spontaneous movements and their relation to the functional adaptation of the nociceptive withdrawal reflexes (NWR) up to postnatal day 22 (P22). Noxious thermal stimulation was used to evoke reflex responses in awake rats. Spontaneous tail movements occurring during active sleep were counted during the first three postnatal weeks and classified into two major classes: simple movements (unidirectional) and complex twitches (bi-directional and oscillating). All spinal nerves caudal to L2 were cut at P12 to study the effect of deafferentation on spontaneous movements. The number of simple movements and complex twitches in the deafferented animals did not differ as compared to control animals. The adaptation of tail NWR occurred during the period P7-P22. Spontaneous tail movements occurred relatively frequently and overlapped in time the adaptation of NWR. Notably, the relative number of simple movements increased in parallel with the functional adaptation of the NWR, suggesting a role of simple twitches in NWR adaptation. The present findings indicate that the spontaneous movements studied are driven by intrinsic mechanisms in the CNS and suggest that sensory feedback does not influence the spontaneous movement patterns. Moreover, the NWR adaptation appears to be related to a qualitative change in spontaneous movements caused by maturation in spinal reflex circuit connections.

Time course of cerebellar morphological development in postnatal ferrets: ontogenetic and comparative perspectives.

We provide the first systematic description of the morphological ontogenesis of the ferret cerebellum and compare its relative time-course to that of the rat cerebellum. Overall cerebellar size, foliation, and thickness of cortical layers were quantified and Purkinje cell morphology was characterized at 24 timepoints in ferrets from postnatal day (P)1 to P63. The ferret cerebellum was substantially larger than that of the rat and had a much longer developmental period. In ferrets, Purkinje cells were dispersed into a monolayer by P9, the formation of folia declined abruptly around P20, and the external granular layer peaked in thickness around P22 and disappeared by P56. Timepoints of corresponding relative developmental maturity of the quantified architectural features of rat and ferret cerebella were determined and their relationship was analyzed by linear regression. The time-conversion equation derived, describing the relationship between cerebellar morphogenesis in the two species, had a determination coefficient (r2) of 0.95. Conspicuously, the equation predicted with high accuracy the timing of structural changes in individual Purkinje cells in the ferret cerebellum. The conversion equation should be useful for precise quantitative translation of data between studies of ferret and rat cerebellum and for comparisons between development of motor and sensory structures and functions in ferrets. The degree of similarity in the time-courses of cerebellar development in two distantly related mammals makes explicit in quantitative terms how remarkably conserved the cerebellum is in phylogenesis. Therefore, the methodology should be applicable to precise quantitative conversions of cerebellar developmental time-courses also between other species.

Ontogenesis of within-session locomotor habituation in the open field.

Habituation signifies a decreased response to a constant or repeated stimulus or environment. Although habituation is a fundamental form of nonassociative learning, little is known about its ontogenesis. Here, locomotor activity of postnatal ferrets within individual open field sessions was quantitatively analysed. The patterns of activity revealed a gradual shift across developmental time between relative increment and decrement of activity within sessions. The increment-to-decrement turning point was around postnatal day 48. These novel findings indicate that systematic changes in the interplay between mechanisms that drive exploratory behaviour and those that inhibit it shape the ontogenesis of open field habituation. The remarkable robustness of the data underscores the suitability of the ferret as an experimental animal for investigating ontogenesis of habituation.

Time course of postnatal motor development in ferrets: ontogenetic and comparative perspectives.

We assess relative time courses of motor development in ferrets and rats and evaluate ferrets as experimental animals for studies of motor development. Motor behaviour of ferret pups was characterized in daily sessions from postnatal day (P) 2 to P63. Observations concerning rotational locomotion ('pivoting'), crawling, walking, upright standing ('rearing') and walking on a narrow path; righting on a surface, in mid-air and on an inclined plane ('geotaxis') were quantified in detail and compared with published data on rat motor development. Besides providing a comprehensive characterization of ferret motor development, our results demonstrate that relative time courses of emergence of motor skills in ferrets and rats are highly similar despite substantially different duration of postnatal periods. The relationship between species was determined by linear regression analysis of an x-y-plot of postnatal ages (y: ferret days; x: rat days) corresponding to given levels of performance of specific skills. The model equation y = 2.46x-4.18 represents the conversion between time courses of rat and ferret motor development. Remarkably, the model explained 81% of data variance (r2 = 0.81) and should hence be useful for translation of motor developmental data between ferret and rat and for comparisons between motor and other functions in ferrets. The highly conserved relative time course also has more general implications for the understanding of comparative aspects of development. In addition, the high reproducibility of data within the present study underscores the suitability of the ferret as an experimental animal for studies of motor development.