Comparing the development of cortex-wide gene expression patterns between two species in a common reference frame.

Advances in sequencing techniques have made comparative studies of gene expression a current focus for understanding evolutionary and developmental processes. However, insights into the spatial expression of genes have been limited by a lack of robust methodology. To overcome this obstacle, we developed methods and software tools for quantifying and comparing tissue-wide spatial patterns of gene expression within and between species. Here, we compare cortex-wide expression of RZRß and Id2 mRNA across early postnatal development in mice and voles. We show that patterns of RZRß expression in neocortical layer 4 are highly conserved between species but develop rapidly in voles and much more gradually in mice, who show a marked expansion in the relative size of the putative primary visual area across the first postnatal week. Patterns of Id2 expression, by contrast, emerge in a dynamic and layer-specific sequence that is consistent between the two species. We suggest that these differences in the development of neocortical patterning reflect the independent evolution of brains, bodies, and sensory systems in the 35 million years since their last common ancestor.

Hippocampal, Whole Midbrain, Red Nucleus, and Ventral Tegmental Area Volumes Are Increased by Selective Breeding for High Voluntary Wheel-Running Behavior.

Uncovering relationships between neuroanatomy, behavior, and evolution are important for understanding the factors that control brain function. Voluntary exercise is one key behavior that both affects, and may be affected by, neuroanatomical variation. Moreover, recent studies suggest an important role for physical activity in brain evolution. We used a unique and ongoing artificial selection model in which mice are bred for high voluntary wheel-running behavior, yielding four replicate lines of high runner (HR) mice that run ∼3-fold more revolutions per day than four replicate nonselected control (C) lines. Previous studies reported that, with body mass as a covariate, HR mice had heavier whole brains, non-cerebellar brains, and larger midbrains than C mice. We sampled mice from generation 66 and used high-resolution microscopy to test the hypothesis that HR mice have greater volumes and/or cell densities in nine key regions from either the midbrain or limbic system. In addition, half of the mice were given 10 weeks of wheel access from weaning, and we predicted that chronic exercise would increase the volumes of the examined brain regions via phenotypic plasticity. We replicated findings that both selective breeding and wheel access increased total brain mass, with no significant interaction between the two factors. In HR compared to C mice, adjusting for body mass, both the red nucleus (RN) of the midbrain and the hippocampus (HPC) were significantly larger, and the whole midbrain tended to be larger, with no effect of wheel access nor any interactions. Linetype and wheel access had an interactive effect on the volume of the periaqueductal gray (PAG), such that wheel access increased PAG volume in C mice but decreased volume in HR mice. Neither linetype nor wheel access affected volumes of the substantia nigra, ventral tegmental area, nucleus accumbens, ventral pallidum (VP), or basolateral amygdala. We found no main effect of either linetype or wheel access on neuronal densities (numbers of cells per unit area) for any of the regions examined. Taken together, our results suggest that the increased exercise phenotype of HR mice is related to increased RN and hippocampal volumes, but that chronic exercise alone does not produce such phenotypes.

The Impact of Paternal Alcohol Consumption on Offspring Brain and Behavioral Development.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) describe the wide array of long-lasting developmental abnormalities in offspring due to prenatal alcohol (ethanol [EtOH]) exposure via maternal gestational drinking. Although the teratogenic consequences of prenatal EtOH exposure, are apparent, the effects of preconception paternal EtOH exposure (PatEE) are still unclear. Previous research suggests that PatEE can induce molecular changes and abnormal behavior in the offspring. However, it is not known whether PatEE impacts the development of the neocortex and behavior in offspring as demonstrated in maternal consumption models of FASD (J Neurosci, 33, 2013, 18893). METHODS: In this study, we utilized a novel mouse model of PatEE where male mice self-administered 25% EtOH for an extended period prior to conception, generating indirect exposure to the offspring through the paternal germline. Following mating, we examined the effects of PatEE on offspring neocortical development at postnatal day (P) 0 and evaluated several aspects of behavior at both P20 and P30 using a battery of behavioral assays. RESULTS: PatEE resulted in significant impact on neocortical development, including abnormal patterns of gene expression within the neocortex at P0 and subtle alterations in patterns of intraneocortical connections. Additionally, PatEE mice exhibited a sex-specific increase in activity and sensorimotor integration deficits at P20, and decreased balance, coordination, and short-term motor learning at P30. This suggests that PatEE may generate long-lasting, sex-specific effects on offspring behavior. CONCLUSIONS: These results demonstrate that the developmental impact of preconception PatEE is more harmful than previously thought and provide additional insights into the biological mechanisms that may underlie atypical behavior observed in children of alcoholic fathers.

Prenatal Ethanol Exposure and Neocortical Development: A Transgenerational Model of FASD.

Fetal Alcohol Spectrum Disorders, or FASD, represent a range of adverse developmental conditions caused by prenatal ethanol exposure (PrEE) from maternal consumption of alcohol. PrEE induces neurobiological damage in the developing brain leading to cognitive-perceptual and behavioral deficits in the offspring. Alcohol-mediated alterations to epigenetic function may underlie PrEE-related brain dysfunction, with these changes potentially carried across generations to unexposed offspring. To determine the transgenerational impact of PrEE on neocortical development, we generated a mouse model of FASD and identified numerous stable phenotypes transmitted via the male germline to the unexposed third generation. These include alterations in ectopic intraneocortical connectivity, upregulation of neocortical Rzrß and Id2 expression accompanied by both promoter hypomethylation of these genes and decreased global DNA methylation levels. DNMT expression was also suppressed in newborn PrEE cortex, providing further insight into how ethanol perturbs DNA methylation leading to altered regulation of gene transcription. These PrEE-induced, transgenerational phenotypes may be responsible for cognitive, sensorimotor, and behavioral deficits seen in humans with FASD. Thus, understanding the possible epigenetic mechanisms by which these phenotypes are generated may reveal novel targets for therapeutic intervention of FASD and lead to advances in human health.

The Impact of Prenatal Ethanol Exposure on Neuroanatomical and Behavioral Development in Mice.

BACKGROUND: In utero alcohol, or ethanol (EtOH), exposure produces developmental abnormalities in the brain of the fetus, which can result in lifelong behavioral abnormalities. Fetal alcohol spectrum disorders (FASD) is a term used to describe a range of adverse developmental conditions caused by EtOH exposure during gestation. Children diagnosed with FASD potentially exhibit a host of phenotypes including growth retardation, facial dysmorphology, central nervous system anomalies, abnormal behavior, and cognitive deficits. Previous research suggests that abnormal gene expression and circuitry in the neocortex may underlie reported disabilities of learning, memory, and behavior resulting from early exposure to alcohol (J Neurosci, 33, 2013, 18893). METHODS: Here, we utilize a mouse model of FASD to examine effects of prenatal EtOH exposure (PrEE), on brain anatomy in newborn (postnatal day [P]0), weanling (P20), and early adult (P50) mice. We correlate abnormal cortical and subcortical anatomy with atypical behavior in adult P50 PrEE mice. In this model, experimental dams self-administered a 25% EtOH solution throughout gestation (gestational days 0 to 19, day of birth), generating the exposure to the offspring. RESULTS: Results from these experiments reveal long-term alterations to cortical anatomy, including atypical developmental cortical thinning, and abnormal subcortical development as a result of in utero EtOH exposure. Furthermore, offspring exposed to EtOH during the prenatal period performed poorly on behavioral tasks measuring sensorimotor integration and anxiety. CONCLUSIONS: Insight from this study will help provide new information on developmental trajectories of PrEE and the biological etiologies of abnormal behavior in people diagnosed with FASD.

Prenatal ethanol exposure disrupts intraneocortical circuitry, cortical gene expression, and behavior in a mouse model of FASD.

In utero ethanol exposure from a mother's consumption of alcoholic beverages impacts brain and cognitive development, creating a range of deficits in the child (Levitt, 1998; Lebel et al., 2012). Children diagnosed with fetal alcohol spectrum disorders (FASD) are often born with facial dysmorphology and may exhibit cognitive, behavioral, and motor deficits from ethanol-related neurobiological damage in early development. Prenatal ethanol exposure (PrEE) is the number one cause of preventable mental and intellectual dysfunction globally, therefore the neurobiological underpinnings warrant systematic research. We document novel anatomical and gene expression abnormalities in the neocortex of newborn mice exposed to ethanol in utero. This is the first study to demonstrate large-scale changes in intraneocortical connections and disruption of normal patterns of neocortical gene expression in any prenatal ethanol exposure animal model. Neuroanatomical defects and abnormal neocortical RZRß, Id2, and Cadherin8 expression patterns are observed in PrEE newborns, and abnormal behavior is present in 20-d-old PrEE mice. The vast network of neocortical connections is responsible for high-level sensory and motor processing as well as complex cognitive thought and behavior in humans. Disruptions to this network from PrEE-related changes in gene expression may underlie some of the cognitive-behavioral phenotypes observed in children with FASD.

Consumption habits of pregnant women and implications for developmental biology: a survey of predominantly Hispanic women in California.

BACKGROUND: Healthy post-pregnancy outcomes are contingent upon an informed regimen of prenatal care encouraging healthy maternal consumption habits. In this article, we describe aspects of maternal intake of food, drink, and medication in a population of predominantly Hispanic women in Southern California. Potential implications for unhealthy prenatal dietary choices are discussed. METHODS: The Food, Beverage, and Medication Intake Questionnaire (FBMIQ) measures common practices of maternal consumption during pregnancy. The FBMIQ was administered to English and Spanish speaking pregnant and recently pregnant (36 weeks pregnant - 8 weeks post-partum) women over the age of 18 who were receiving care from a private medical group in Downey CA. RESULTS: A total of 200 women completed the FBMIQ. Consumption habits of healthy foods and beverages, unhealthy foods, unhealthy beverages, and medication are characterized in this article. Data indicate widespread consumption of fresh fruit, meats, milk and juice and indicate most women used prenatal vitamin supplements. Studies in developmental neuroscience have shown that certain substances may cause teratogenic effects on the fetus when ingested by the mother during pregnancy. Those potentially harmful substances included in our study were Bisphenol-A (BPA), methylmercury, caffeine, alcohol and certain medications. Our results show that a proportion of the women surveyed in our study consumed BPA, methylmercury, caffeine, alcohol, and certain medications at varied levels during pregnancy. This represents an interesting finding and suggests a disconnect between scientific data and general recommendations provided to pregnant mothers by obstetricians. CONCLUSIONS: The results of our study demonstrate that a proportion of pregnant women consume substances that are potentially teratogenic and may impact the health and well being of the offspring. It is important to appraise healthy and unhealthy consumption habits in order to encourage healthy practices and alleviate future effects of preventable, toxin-induced developmental issues. Prenatal advising should discourage the consumption of dangerous foods, beverages, and medications that women commonly report eating during pregnancy.

Alcohol and lactation: Developmental deficits in a mouse model.

It is well documented that prenatal ethanol exposure via maternal consumption of alcohol during pregnancy alters brain and behavioral development in offspring. Thus, the Centers for Disease Control (CDC) advises against maternal alcohol consumption during pregnancy. However, little emphasis has been placed on educating new parents about alcohol consumption while breastfeeding. This is partly due to a paucity of research on lactational ethanol exposure (LEE) effects in children; although, it has been shown that infants exposed to ethanol via breast milk frequently present with reduced body mass, low verbal IQ scores, and altered sleeping patterns. As approximately 36% of breastfeeding mothers in the US consume alcohol, continued research in this area is critical. Our study employed a novel murine LEE model, where offspring were exposed to ethanol via nursing from postnatal day (P) 6 through P20, a period correlated with infancy in humans. Compared to controls, LEE mice had reduced body weights and neocortical lengths at P20 and P30. Brain weights were also reduced in both ages in males, and at P20 for females, however, female brain weights recovered to control levels by P30. We investigated neocortical features and found that frontal cortex thickness was reduced in LEE males compared to controls. Analyses of dendritic spines in the prelimbic subdivision of medial prefrontal cortex revealed a trend of reduced densities in LEE mice. Results of behavioral tests suggest that LEE mice engage in higher risk-taking behavior, show abnormal stress regulation, and exhibit increased hyperactivity. In summary, our data describe potential adverse brain and behavioral developmental outcomes due to LEE. Thus, women should be advised to refrain from consuming alcohol during breastfeeding until additional research can better guide recommendations of safe maternal practices in early infancy.

A lifespan analysis of intraneocortical connections and gene expression in the mouse I.

A hallmark of mammalian evolution is the structural and functional complexity of the cerebral cortex. Within the cerebral cortex, the neocortex, or isocortex, is a 6-layered complexly organized structure that is comprised of multiple interconnected sensory and motor areas. These areas and their precise patterns of connections arise during development, through a process termed arealization. Intrinsic, activity-independent and extrinsic, activity-dependent mechanisms are involved in the development of neocortical areas and their connections. The intrinsic molecular mechanisms involved in the establishment of this sophisticated network are not fully understood. In this report (I) and the companion report (II), we present the first lifespan analysis of ipsilateral intraneocortical connections (INCs) among multiple sensory and motor regions, from the embryonic period to adulthood in the mouse. Additionally, we characterize the neocortical expression patterns of several developmentally regulated genes that are of central importance to studies investigating the molecular control of arealization from embryonic day 13.5 to postnatal day (P) 3 (I) and P6 to 50 (II). In this analysis, we utilize novel methods to correlate the boundaries of gene expression with INCs and developing areal boundaries, in order to better understand the nature of gene-areal relationships during development.

A lifespan analysis of intraneocortical connections and gene expression in the mouse II.

The mammalian neocortex contains an intricate processing network of multiple sensory and motor areas that allows the animal to engage in complex behaviors. These anatomically and functionally unique areas and their distinct connections arise during early development, through a process termed arealization. Both intrinsic, activity-independent and extrinsic, activity-dependent mechanisms drive arealization, much of which occurs during the areal patterning period (APP) from late embryogenesis to early postnatal life. How areal boundaries and their connections develop and change from infancy to adulthood is not known. Additionally, the adult patterns of sensory and motor ipsilateral intraneocortical connections (INCs) have not been thoroughly characterized in the mouse. In this report and its companion (I), we present the first lifespan analysis of ipsilateral INCs among multiple sensory and motor regions in mouse. We describe the neocortical expression patterns of several developmentally regulated genes that are of central importance to studies investigating the molecular regulation of arealization, from postnatal day (P) 6 to P50. In this study, we correlate the boundaries of gene expression patterns with developing areal boundaries across a lifespan, in order to better understand the nature of gene-areal relationships from early postnatal life to adulthood.

Transgenerational Effects of Prenatal Ethanol Exposure in Prepubescent Mice.

Background: Fetal alcohol spectrum disorders (FASD) represent a leading cause of non-genetic neuropathologies. Recent preclinical evidence from suggests that prenatal ethanol exposure (PrEE), like other environmental exposures, may have a significant, transgenerational impact on the offspring of directly exposed animals, including altered neocortical development at birth and behavior in peri-pubescent mice. How these adverse behavioral outcomes are manifested within the brain at the time of behavioral disruption remains unknown. Methods: A transgenerational mouse model of FASD was used to generate up to a third filial generation of offspring to study. Using a multi-modal battery of behavioral assays, we assessed motor coordination/function, sensorimotor processing, risk-taking behavior, and depressive-like behavior in postnatal day (P) 20 pre-pubescent mice. Additionally, sensory neocortical area connectivity using dye tracing, neocortical gene expression using in situ RNA hybridization, and spine density of spiny stellate cells in the somatosensory cortex using Golgi-Cox staining were examined in mice at P20. Results: We found that PrEE induces behavioral abnormalities including abnormal sensorimotor processing, increased risk-taking behavior, and increased depressive-like behaviors that extend to the F3 generation in 20-day old mice. Assessment of both somatosensory and visual cortical connectivity, as well as cortical RZRß expression in pre-pubescent mice yielded no significant differences among any experimental generations. In contrast, only directly-exposed F1 mice displayed altered cortical expression of Id2 and decreased spine density among layer IV spiny stellate cells in somatosensory cortex at this pre-pubescent, post weaning age. Conclusion: Our results suggest that robust, clinically-relevant behavioral abnormalities are passed transgenerationally to the offspring of mice directly exposed to prenatal ethanol. Additionally, in contrast to our previous findings in the newborn PrEE mouse, a lack of transgenerational findings within the brain at this later age illuminates the critical need for future studies to attempt to discover the link between neurological function and the described behavioral changes. Overall, our study suggests that multi-generational effects of PrEE may have a substantial impact on human behavior as well as health and well-being and that these effects likely extend beyond early childhood.

Rescue of ethanol-induced FASD-like phenotypes via prenatal co-administration of choline.

Maternal consumption of alcohol during pregnancy can generate a multitude of deficits in the offspring. Fetal Alcohol Spectrum Disorders, or FASD, describe a palette of potentially life-long phenotypes that result from exposure to ethanol during human gestation. There is no cure for FASD and cognitive-behavioral therapies typically have low success rates, especially in severe cases. The neocortex, responsible for complex cognitive and behavioral function, is altered by prenatal ethanol exposure (PrEE). Supplementation with choline, an essential nutrient, during the prenatal ethanol insult has been associated with a reduction of negative outcomes associated with PrEE. However, choline's ability to prevent deficits within the developing neocortex, as well as the underlying mechanisms, remain unclear. Here, we exposed pregnant mice to 25% ethanol in addition to a 642 mg/L choline chloride supplement throughout gestation to determine the impact of choline supplementation on neocortical and behavioral development in ethanol-exposed offspring. We found that concurrent choline supplementation prevented gross developmental abnormalities associated with PrEE including reduced body weight, brain weight, and cortical length as well as partially ameliorated PrEE-induced abnormalities in intraneocortical circuitry. Additionally, choline supplementation prevented altered expression of RZRß and Id2, two genes implicated in postmitotic patterning of neocortex, and global DNA hypomethylation within developing neocortex. Lastly, choline supplementation prevented sensorimotor behavioral dysfunction and partially ameliorated increased anxiety-like behavior observed in PrEE mice, as assessed by the Suok and Ledge tests. Our results suggest that choline supplementation may represent a potent preventative measure for the adverse outcomes associated with PrEE.

Early postnatal gene expression in the developing neocortex of prairie voles (Microtus ochrogaster) is related to parental rearing style.

The earliest and most prevalent sensory experience includes tactile, thermal, and olfactory stimulation delivered to the young via contact with the mother, and in some mammals, the father. Prairie voles (Microtus ochrogaster), like humans, are biparental and serve as a model for understanding the impact of parent/offspring interactions on the developing brain. Prairie voles also exhibit natural variation in the level of tactile stimulation delivered by the parents to the offspring, and this has been well documented and quantified. Previous studies revealed that adult prairie vole offspring who received either high (HC) or low (LC) tactile contact from their parents have differences in the size of cortical fields and the connections of somatosensory cortex. In the current investigation, we examined gene expression, intraneocortical connectivity, and cortical thickness in newborn voles to appreciate when differences in HC and LC offspring begin to emerge. We observed differences in developmentally regulated genes, as well as variation in prelimbic and anterior cingulate cortical thickness at postnatal Day 1 (P1) in HC and LC voles. Results from this study suggest that parenting styles, such as those involving high or low physical contact, impact the developing neocortex via very early sensory experience as well as differences in epigenetic modifications that may emerge in HC and LC voles.

Long-Lasting Effects of Prenatal Ethanol Exposure on Fear Learning and Development of the Amygdala.

Prenatal ethanol exposure (PrEE) produces developmental abnormalities in brain and behavior that often persist into adulthood. We have previously reported abnormal cortical gene expression, disorganized neural circuitry along with deficits in sensorimotor function and anxiety in our CD-1 murine model of fetal alcohol spectrum disorders, or FASD (El Shawa et al., 2013; Abbott et al., 2016). We have proposed that these phenotypes may underlie learning, memory, and behavioral deficits in humans with FASD. Here, we evaluate the impact of PrEE on fear memory learning, recall and amygdala development at two adult timepoints. PrEE alters learning and memory of aversive stimuli; specifically, PrEE mice, fear conditioned at postnatal day (P) 50, showed deficits in fear acquisition and memory retrieval when tested at P52 and later at P70-P72. Interestingly, this deficit in fear acquisition observed during young adulthood was not present when PrEE mice were conditioned later, at P80. These mice displayed similar levels of fear expression as controls when tested on fear memory recall. To test whether PrEE alters development of brain circuitry associated with fear conditioning and fear memory recall, we histologically examined subdivisions of the amygdala in PrEE and control mice and found long-term effects of PrEE on fear memory circuitry. Thus, results from this study will provide insight on the neurobiological and behavioral effects of PrEE and provide new information on developmental trajectories of brain dysfunction in people prenatally exposed to ethanol.

Fgf8 regulates the development of intra-neocortical projections.

The process of generating functionally distinct neocortical areas requires the formation of an intra-neocortical connectivity map. Here, we explore the early development of murine intra-neocortical projections and find that axons from rostral and caudal neurons remain, respectively, within large rostral and caudal domains of the neonatal neocortex. Despite evidence that thalamic input can regulate neocortical areal properties, we found that the neonatal intra-neocortical projection pattern was not perturbed when thalamic input was absent in Gbx2 mutants. On the contrary, in Fgf8 hypomorphic mutants, the rostral neocortex of which acquires more caudal molecular properties, caudally located neurons ectopically project axons into the rostral cortex. Therefore, neocortical patterning by Fgf8 also contributes to arealization through mediating early development of intra-neocortical connectivity.

Rapid Changes in Cortical and Subcortical Brain Regions after Early Bilateral Enucleation in the Mouse.

Functional sensory and motor areas in the developing mammalian neocortex are formed through a complex interaction of cortically intrinsic mechanisms, such as gene expression, and cortically extrinsic mechanisms such as those mediated by thalamic input from the senses. Both intrinsic and extrinsic mechanisms are believed to be involved in cortical patterning and the establishment of areal boundaries in early development; however, the nature of the interaction between intrinsic and extrinsic processes is not well understood. In a previous study, we used a perinatal bilateral enucleation mouse model to test some aspects of this interaction by reweighting sensory input to the developing cortex. Visual deprivation at birth resulted in a shift of intraneocortical connections (INCs) that aligned with ectopic ephrin A5 expression in the same location ten days later at postnatal day (P) 10. A prevailing question remained: Does visual deprivation first induce a change in gene expression, followed by a shift in INCs, or vice versa? In the present study, we address this question by investigating the neuroanatomy and patterns of gene expression in post-natal day (P) 1 and 4 mice following bilateral enucleation at birth. Our results demonstrate a rapid reduction in dorsal lateral geniculate nucleus (dLGN) size and ephrin A5 gene expression 24-hours post-enucleation, with more profound effects apparent at P4. The reduced nuclear size and diminished gene expression mirrors subtle changes in ephrin A5 expression evident in P1 and P4 enucleated neocortex, 11 and 8 days prior to natural eye opening, respectively. Somatosensory and visual INCs were indistinguishable between P1 and P4 mice bilaterally enucleated at birth, indicating that perinatal bilateral enucleation initiates a rapid change in gene expression (within one day) followed by an alteration of sensory INCs later on (second postnatal week). With these results, we gain a deeper understanding of how gene expression and sensory input together regulate cortical arealization and plasticity during early development.

The effects of lifelong blindness on murine neuroanatomy and gene expression.

Mammalian neocortical development is regulated by neural patterning mechanisms, with distinct sensory and motor areas arising through the process of arealization. This development occurs alongside developing central or peripheral sensory systems. Specifically, the parcellation of neocortex into specific areas of distinct cytoarchitecture, connectivity and function during development is reliant upon both cortically intrinsic mechanisms, such as gene expression, and extrinsic processes, such as input from the sensory receptors. This developmental program shifts from patterning to maintenance as the animal ages and is believed to be active throughout life, where the brain's organization is stable yet plastic. In this study, we characterize the long-term effects of early removal of visual input via bilateral enucleation at birth. To understand the long-term effects of early blindness we conducted anatomical and molecular assays 18 months after enucleation, near the end of lifespan in the mouse. Bilateral enucleation early in life leads to long-term, stable size reductions of the thalamic lateral geniculate nucleus (LGN) and the primary visual cortex (V1) alongside a increase in individual whisker barrel size. Neocortical gene expression in the aging brain has not been previously identified; we document cortical expression of multiple regionalization genes. Expression patterns of Ephrin A5, COUP-TFI, and RZRß and patterns of intraneocortical connectivity (INC) are altered in the neocortices of aging blind mice. Sensory inputs from different modalities during development likely play a major role in the development of cortical areal and thalamic nuclear boundaries. We suggest that early patterning by prenatal retinal activity combined with persistent gene expression within the thalamus and cortex is sufficient to establish and preserve a small but present LGN and V1 into late adulthood.

Organization of area 3a in macaque monkeys: contributions to the cortical phenotype.

The detailed organization of somatosensory area 3a was examined in macaque monkeys using multiunit electrophysiological recording techniques. By examining topographic relationships, changes in receptive field size, and the type of stimulus that neurons responded to, functional boundaries of area 3a were determined and related to architectonic boundaries. One striking observation was that the location of area 3a varied with respect to the central sulcus. In one-half of the cases area 3a was on the rostral bank and fundus of the central sulcus and in the other half of the cases it was on the caudal bank and fundus of the central sulcus. In terms of topographic organization, we found that area 3a contains a complete representation of deep receptors and musculature of the contralateral body, and that the general organization of body part representations mirrors that of the primary somatosensory area, 3b. These results as well as results from studies of area 3a in ours and other laboratories indicate that area 3a is part of a network involved in proprioception, postural control, and the generation of coordinated movements. Further, comparative analysis of area 3a in a variety of species suggests that its construction is based, to a large extent, on the use of a particular body part rather than on innervation density.

Brain and cognitive evolution: forms of modularity and functions of mind.

Genetic and neurobiological research is reviewed as related to controversy over the extent to which neocortical organization and associated cognitive functions are genetically constrained or emerge through patterns of developmental experience. An evolutionary framework that accommodates genetic constraint and experiential modification of brain organization and cognitive function is then proposed. The authors argue that 4 forms of modularity and 3 forms of neural and cognitive plasticity define the relation between genetic constraint and the influence of developmental experience. For humans, the result is the ontogenetic emergence of functional modules in the domains of folk psychology, folk biology, and folk physics. The authors present a taxonomy of these modules and review associated research relating to brain and cognitive plasticity in these domains.

Prenatal nicotine exposure increases anxiety and modifies sensorimotor integration behaviors in adult female mice.

Prenatal exposure to nicotine (PNE) has been associated with a myriad of physiological, cognitive, and behavioral effects in the developing offspring. In this study, CD-1 dams were given injections of nicotine or control vehicle throughout gestation and their offspring were raised to 6 months of age. Adult mice were administered a battery of behavioral tests (the Suok test, the elevated platform test, and the elevated plus maze test) to assess anxiety and sensorimotor integration. PNE resulted in a decreased likelihood of jumping during the elevated platform test and decreased directed exploration in the Suok test, both indicative of increased anxiety. Also, PNE mice showed increased numbers of missteps while traversing an elevated rod in the Suok test, demonstrating altered sensorimotor integration. No significant differences were found in falls, segments traveled, latency to leave the central zone, vegetative responses, risk assessment behaviors, or autogroom behaviors. The elevated plus maze test revealed no significant differences between groups. No significant differences in body and brain weights, or cortical thickness within motor, somatosensory, and visual cortices were observed between PNE and control mice. Although neuroanatomical effects of PNE may be rescued as development progresses, defects in sensorimotor integration and increased anxiety persist into adulthood.