Adele M. H. Seelke

Topographic Maps within Brodmann's Area 5 of Macaque Monkeys

Brodmanns area 5 has traditionally included the rostral bank of the intraparietal sulcus (IPS) as well as posterior portions of the postcentral gyrus and medial wall. However, different portions of this large architectonic zone may serve different functions related to reaching and grasping behaviors. The current study used multiunit recording techniques in anesthetized macaque monkeys to survey a large extent of the rostral bank of the IPS so that hundreds of recording sites could be used to determine the functional subdivisions and topographic organization of cortical areas in this region. We identified a lateral area on the rostral IPS that we term area 5L. Area 5L contains neurons with receptive fields on mostly the shoulder, forelimb, and digits, with no apparent representation of other body parts. Thus, there is a large magnification of the forelimb. Receptive fields for neurons in this region often contain multiple joints of the forelimb or multiple digits, which results in imprecise topography or fractures in map organization. Our results provide the first overall topographic map of area 5L obtained in individual macaque monkeys and suggest that this region is distinct from more medial portions of the IPS.

The emergence of somatotopic maps of the body in S1 in rats: the correspondence between functional and anatomical organization.

Most of what we know about cortical map development and plasticity comes from studies in mice and rats, and for the somatosensory cortex, almost exclusively from the whisker-dominated posteromedial barrel fields. Whiskers are the main effector organs of mice and rats, and their representation in cortex and subcortical pathways is a highly derived feature of murine rodents. This specialized anatomical organization may therefore not be representative of somatosensory cortex in general, especially for species that utilize other body parts as their main effector organs, like the hands of primates. For these reasons, we examined the emergence of whole body maps in developing rats using electrophysiological recording techniques. In P5, P10, P15, P20 and adult rats, multiple recordings were made in the medial portion of S1 in each animal. Subsequently, these functional maps were related to anatomical parcellations of S1 based on a variety of histological stains. We found that at early postnatal ages (P5) medial S1 was composed almost exclusively of the representation of the vibrissae. At P10, other body part representations including the hindlimb and forelimb were present, although these were not topographically organized. By P15, a clear topographic organization began to emerge coincident with a reduction in receptive field size. By P20, body maps were adult-like. This study is the first to describe how topography of the body develops in S1 in any mammal. It indicates that anatomical parcellations and functional maps are initially incongruent but become tightly coupled by P15. Finally, because anatomical and functional specificity of developing barrel cortex appears much earlier in postnatal life than the rest of the body, the entire primary somatosensory cortex should be considered when studying general topographic map formation in development.

Individual differences in cortical connections of somatosensory cortex are associated with parental rearing style in prairie voles (Microtus ochrogaster)

Early‐life sensory experiences have a profound effect on brain organization, connectivity, and subsequent behavior. In most mammals, the earliest sensory inputs are delivered to the developing brain through tactile contact with the parents, especially the mother. Prairie voles (Microtus ochrogaster) are monogamous and, like humans, are biparental. Within the normal prairie vole population, both the type and the amount of interactions, particularly tactile contact, that parents have with their offspring vary. The question is whether these early and pervasive differences in tactile stimulation and social experience between parent and offspring are manifest in differences in cortical organization and connectivity. To address this question, we examined the cortical and callosal connections of the primary somatosensory area (S1) in high‐contact (HC) and low‐contact (LC) offspring using neuroanatomical tracing techniques. Injection sites within S1 were matched so that direct comparisons between these two groups could be made. We observed several important differences between these groups. The first was that HC offspring had a greater density of intrinsic connections within S1 compared with LC offspring. Additionally, HC offspring had a more restricted pattern of ipsilateral connections, whereas LC offspring had dense connections with areas of parietal and frontal cortex that were more widespread. Finally, LC offspring had a broader distribution of callosal connections than HC offspring and a significantly higher percentage of labeled callosal neurons. This study is the first to examine individual differences in cortical connections and suggests that individual differences in cortical connections may be related to natural differences in parental rearing styles associated with tactile contact. J. Comp. Neurol. 524:564–577, 2016.

A connection to the past: Monodelphis domestica provides insight into the organization and connectivity of the brains of early mammals

The current experiment is one of a series of comparative studies in our laboratory designed to determine the network of somatosensory areas that are present in the neocortex of the mammalian common ancestor. Such knowledge is critical for appreciating the basic functional circuitry that all mammals possess and how this circuitry was modified to generate species‐specific, sensory‐mediated behavior. Our animal model, the gray short‐tailed opossum (Monodelphis domestica), is a marsupial that is proposed to represent this ancestral state more closely than most other marsupials and, to some extent, even monotremes. We injected neuroanatomical tracers into the primary somatosensory area (S1), rostral and caudal somatosensory fields (SR and SC, respectively), and multimodal cortex (MM) and determined their connections with other architectonically defined cortical fields. Our results show that S1 has dense intrinsic connections, dense projections from the frontal myelinated area (FM), and moderate projections from S2 and SC. SR has strong projections from several areas, including S1, SR, FM, and piriform cortex. SC has dense projections from S1, moderate to strong projections from other somatosensory areas, FM, along with connectivity from the primary (V1) and second visual areas. Finally, MM had dense intrinsic connections, dense projections from SC and V1, and moderate projections from S1. These data support the proposition that ancestral mammals likely had at least four specifically interconnected somatosensory areas, along with at least one multimodal area. We discuss the possibility that these additional somatosensory areas (SC and SR) are homologous to somatosensory areas in eutherian mammals. J. Comp. Neurol. 521:3877–3897, 2013.

Differential changes in the cellular composition of the developing marsupial brain

Throughout development both the body and the brain change at remarkable rates. Specifically, the number of cells in the brain undergoes dramatic nonlinear changes, first exponentially increasing in cell number and then decreasing in cell number. Different cell types, such as neurons and glia, undergo these changes at different stages of development. The current investigation used the isotropic fractionator method to examine the changes in cellular composition at multiple developmental milestones in the short‐tailed opossum, Monodelphis domestica. Here we report several novel findings concerning marsupial brain development and organization. First, during the later stages of neurogenesis (P18), neurons make up most of the cells in the neocortex, although the total number of neurons remains the same throughout the life span. In contrast, in the subcortical regions, the number of neurons decreases dramatically after P18, and a converse relationship is observed for nonneuronal cells. In the cerebellum, the total number of cells gradually increases until P180 and then remains constant, and then the number of neurons is consistent across the developmental ages examined. For the three major structures examined, neuronal density and the percentage of neurons within a structure are highest during neurogenesis and then decrease after this point. Finally, the total number of neurons in the opossum brain is relatively low compared with other small‐brained mammals such as mice. The relatively low number of neurons and correspondingly high number of nonneurons suggests that in the marsupial brain nonneurons may play a significant role in signal processing. J. Comp. Neurol. 521:2602–2620, 2013.

The cellular composition of the marsupial neocortex

In the current investigation we examined the number and proportion of neuronal and non‐neuronal cells in the primary sensory areas of the neocortex of a South American marsupial, the short‐tailed opossum (Monodelphis domestica). The primary somatosensory (S1), auditory (A1), and visual (V1) areas were dissected from the cortical sheet and compared with each other and the remaining neocortex using the isotropic fractionator technique. We found that although the overall sizes of V1, S1, A1, and the remaining cortical regions differed from each other, these divisions of the neocortex contained the same number of neurons, but the remaining cortex contained significantly more non‐neurons than the primary sensory regions. In addition, the percent of neurons was higher in A1 than in the remaining cortex and the cortex as a whole. These results are similar to those seen in non‐human primates. Furthermore, these results indicate that in some respects, such as number of neurons, the neocortex is homogenous across its extent, whereas in other aspects of organization, such as non‐neuronal number and percentage of neurons, there is non‐uniformity. Whereas the overall pattern of neuronal distribution is similar between short‐tailed opossums and eutherian mammals, short‐tailed opossum have a much lower cellular and neuronal density than other eutherian mammals. This suggests that the high neuronal density cortices of mammals such as rodents and primates may be a more recently evolved characteristic that is restricted to eutherians, and likely contributes to the complex behaviors we see in modern mammals. J. Comp. Neurol. 522:2286–2298, 2014.

Localization of oxytocin receptors in the prairie vole (Microtus ochrogaster) neocortex

Early experience and social context interact to alter the phenotype of complex social behaviors. These early experiences can also result in alterations to cortical organization and connections. Given the ability of the neuropeptide oxytocin (OT) to modulate social and reproductive behavior, OT is likely involved in these cortical processes. However, little is known about the distribution of OT and OT receptors (OTR) within the neocortex. Using autoradiographic and neuroanatomical techniques, we characterized the cortical distribution of OT receptors (OTR) in prairie voles, a socially monogamous rodent species. We found that OTR density was low in the primary sensory areas (including primary somatosensory and auditory regions) but was quite high in association regions (including temporal and parietal association areas, and prelimbic regions). In the primary motor area as well as the temporal and parietal association areas, we observed differences in OTR density across cortical layers. Specifically, cortical layers 2/3 and 5 exhibited greater OTR density than layer 4. Our results point to a role for OT in integrating sensory and motor in the prairie vole brain, providing a complementary mechanism for the modulation of social interactions. Given the ability of early social experience and developmental manipulations of OT to affect the brain and behavior, these results suggest a novel mechanism for how OT may influence cortical organization.

Evolution of mammalian sensorimotor cortex: thalamic projections to parietal cortical areas in Monodelphis domestica

The current experiments build upon previous studies designed to reveal the network of parietal cortical areas present in the common mammalian ancestor. Understanding this ancestral network is essential for highlighting the basic somatosensory circuitry present in all mammals, and how this basic plan was modified to generate species specific behaviors. Our animal model, the short-tailed opossum (Monodelphis domestica), is a South American marsupial that has been proposed to have a similar ecological niche and morphology to the earliest common mammalian ancestor. In this investigation, we injected retrograde neuroanatomical tracers into the face and body representations of primary somatosensory cortex (S1), the rostral and caudal somatosensory fields (SR and SC), as well as a multimodal region (MM). Projections from different architectonically defined thalamic nuclei were then quantified. Our results provide further evidence to support the hypothesized basic mammalian plan of thalamic projections to S1, with the lateral and medial ventral posterior thalamic nuclei (VPl and VPm) projecting to S1 body and S1 face, respectively. Additional strong projections are from the medial division of posterior nucleus (Pom). SR receives projections from several midline nuclei, including the medial dorsal, ventral medial nucleus, and Pom. SC and MM show similar patterns of connectivity, with projections from the ventral anterior and ventral lateral nuclei, VPm and VPl, and the entire posterior nucleus (medial and lateral). Notably, MM is distinguished from SC by relatively dense projections from the dorsal division of the lateral geniculate nucleus and pulvinar. We discuss the finding that S1 of the short-tailed opossum has a similar pattern of projections as other marsupials and mammals, but also some distinct projections not present in other mammals. Further we provide additional support for a primitive posterior parietal cortex which receives input from multiple modalities.

Visual acuity in the short-tailed opossum (Monodelphis domestica)

Monodelphis domestica (short-tailed opossum) is an emerging animal model for studies of neural development due to the extremely immature state of the nervous system at birth and its subsequent rapid growth to adulthood. Yet little is known about its normal sensory discrimination abilities. In the present investigation, visual acuity was determined in this species using the optokinetic test (OPT), which relies on involuntary head tracking of a moving stimulus and can be easily elicited using a rotating visual stimulus of varying spatial frequencies. Using this methodology, we determined that the acuity of Monodelphis is 0.58 cycles per degree (cpd), which is similar to the acuity of rats using the same methodology, and higher than in mice. However, acuity in the short-tailed opossum is lower than in other marsupials. This is in part due to the methodology used to determine acuity, but may also be due to differences in diel patterns, lifestyle and phylogeny. We demonstrate that for the short-tailed opossum, the OPT is a rapid and reliable method of determining a baseline acuity and can be used to study enhanced acuities due to cortical plasticity.

Fatherhood alters gene expression within the MPOA

Female parenting is obligate in mammals, but fathering behavior among mammals is rare. Only 3–5% of mammalian species exhibit biparental care, including humans, and mechanisms of fathering behavior remain sparsely studied. However, in species where it does exist, paternal care is often crucial to the survivorship of offspring. The present study is the first to identify new gene targets linked to the experience of fathering behavior in a biparental species using RNA sequencing. In order to determine the pattern of gene expression within the medial preoptic area that is specifically associated with fathering behavior, we identified differentially expressed genes in male prairie voles (Microtus ochrogaster) that experienced one of three social conditions: virgin males, pair bonded males, and males with fathering experience. Differentially expressed genes from each comparison (i.e., Virgin vs Paired, Virgin vs Fathers, and Paired vs Fathers) were evaluated using the Gene Ontology enrichment analysis, and Kegg pathways analysis to reveal metabolic pathways associated with specific differentially expressed genes. Using these tools, we identified a group of genes that are differentially expressed in voles with different amounts of social experience. These genes are involved in a variety of processes, with particular enrichment in genes associated with immune function, metabolism, synaptic plasticity, and the remodeling of dendritic spines. The identification of these genes and processes will lead to novel insights into the biological basis of fathering behavior.