Connections of the perirhinal cortex in the rat brain were studied using anterograde (3H-proline/leucine) and retrograde (horseradish peroxidase) tracers. The perirhinal cortex receives major projections from medial precentral, anterior cingulate, prelimbic, ventral lateral orbital, ventral and posterior agranular insular, temporal, superior and granular parietal, lateral occipital, agranular retrosplenial, and ectorhinal cortices, and from the presubiculum, subiculum, and diagonal band of Broca. Rostral neocortical areas project predominantly to rostral perirhinal regions while more caudal neocortical and subicular areas project predominantly to caudal perirhinal regions. Terminal fields are further segregated within perirhinal cortex to either the dorsal or ventral banks of the rhinal sulcus. All afferents from frontal areas terminate predominantly in the deep layers of its ventral bank; afferents from temporal, parietal, and lateral occipital areas terminate predominantly in the deep and superficial layers along its dorsal bank; and afferents from ectorhinal cortex terminate in a column within its dorsal bank. Cortical cells which project to perirhinal areas are found predominantly in layer II and the superficial part of layer III. However, ventrolateral orbital, parietal, and lateral occipital cortex projections originate predominantly from layer V. Perirhinal areas also receive afferents from the nucleus reuniens of the thalamus, lateral nucleus of the amygdala, claustrum, supramammillary nuclei, and the dorsal raphe nuclei.

The classic anthropological hypothesis known as the "obstetrical dilemma" is a well-known explanation for human altriciality, a condition that has significant implications for human social and behavioral evolution. The hypothesis holds that antagonistic selection for a large neonatal brain and a narrow, bipedal-adapted birth canal poses a problem for childbirth; the hominin "solution" is to truncate gestation, resulting in an altricial neonate. This explanation for human altriciality based on pelvic constraints persists despite data linking human life history to that of other species. Here, we present evidence that challenges the importance of pelvic morphology and mechanics in the evolution of human gestation and altriciality. Instead, our analyses suggest that limits to maternal metabolism are the primary constraints on human gestation length and fetal growth. Although pelvic remodeling and encephalization during hominin evolution contributed to the present parturitional difficulty, there is little evidence that pelvic constraints have altered the timing of birth.bipedalism | EGG hypothesis | energetics | metabolic crossover hypothesis | pregnancy E utherian mammals vary widely in their degree of development at birth. Altricial species (e.g., rodents and some carnivores) are characterized by a large number of littermates and short gestation lengths, resulting in relatively undeveloped brains, a lack of specialization in corporal development, and feebleness at birth. Altricial neonates are usually hairless and dependent on external sources for warmth, and their sensory organs are often closed. In contrast, precocial species (e.g., bovids, equids, cetaceans) are born when they are highly developed with fully open and operating sensory organs. Immediately after birth, precocial neonates begin behaving similarly to adults in movement, sensory perception, and communication. Neonate development is thought to reflect each species' evolved maternal investment strategy, as well as environmental pressures, such as resource availability and predation risk (1-3).Humans differ from other primates in terms of neonatal development. Our neonates are born with the least-developed brains of any primate, with brains less than 30% of adult size (4). As a result, although human newborns are precocial in other respects, our neonates are neurologically and behaviorally altricial. Portmann (5) coined the term "secondary altriciality" to describe the distinct state of human neonates compared with the kind of primary or primitive altriciality experienced by other mammals and derived with respect to primate precociality. He estimated that instead of 9 mo, a gestation period of 18-21 mo would be required for humans to be born at neurological and cognitive developmental stage equivalent to that achieved by a chimpanzee neonate (see also ref. 6).Human altriciality has long been seen as an important hominin trait, not just because of its departure from the other primates but because of the reproductive and social strategies that vulnerable ...

The movement disorder in Parkinson's disease results from the selective degeneration of a small group of dopaminergic neurons in the substantia nigra pars compacta region of the brain. A number of exploratory studies using human fetal tissue allografts have suggested that transplantation of dopaminergic neurons may become an effective treatment for patients with Parkinson's disease and the difficulty in obtaining human fetal tissue has generated interest in finding corresponding non-human donor cells. Here we report a post-mortem histological analysis of fetal pig neural cells that were placed unilaterally into the caudate-putamen brain region of a patient suffering from Parkinson's disease. Long-term (over seven months) graft survival was found and the presence of pig dopaminergic neurons and other pig neural and glial cells is documented. Pig neurons extended axons from the graft sites into the host brain. Furthermore, other graft derived cells were observed several millimeters from the implantation sites. Markers for human microglia and T-cells showed only low reactivity in direct proximity to the grafts. This is the first documentation of neural xenograft survival in the human brain and of appropriate growth of non-human dopaminergic neurons for a potential therapeutic response in Parkinson's disease.

Neural and stem cell transplantation is emerging as a potential treatment for neurodegenerative diseases. Transplantation of specific committed neuroblasts (fetal neurons) to the adult brain provides such scientific exploration of these new potential therapies. Huntington's disease (HD) is a fatal, incurable autosomal dominant (CAG repeat expansion of huntingtin protein) neurodegenerative disorder with primary neuronal pathology within the caudate-putamen (striatum). In a clinical trial of human fetal striatal tissue transplantation, one patient died 18 months after transplantation from cardiovascular disease, and postmortem histological analysis demonstrated surviving transplanted cells with typical morphology of the developing striatum. Selective markers of both striatal projection and interneurons such as dopamine and c-AMP-related phosphoprotein, calretinin, acetylcholinesterase, choline acetyltransferase, tyrosine hydroxylase, calbindin, enkephalin, and substance P showed positive transplant regions clearly innervated by host tyrosine hydroxylase fibers. There was no histological evidence of immune rejection including microglia and macrophages. Notably, neuronal protein aggregates of mutated huntingtin, which is typical HD neuropathology, were not found within the transplanted fetal tissue. Thus, although there is a genetically predetermined process causing neuronal death within the HD striatum, implanted fetal neural cells lacking the mutant HD gene may be able to replace damaged host neurons and reconstitute damaged neuronal connections. This study demonstrates that grafts derived from human fetal striatal tissue can survive, develop, and are unaffected by the disease process, at least for 18 months, after transplantation into a patient with HD. R ecent findings in genetics, stem cell biology, and neural transplantation suggest that brain repair will be possible for the treatment of neurodegenerative diseases (1, 2). Before initiating large clinical trials that test the efficacy of novel donor cells, it is important to determine the clinical feasibility of such cell-based therapies. Transplantation of specific committed neuroblasts (fetal neurons) to the adult human brain provides such a scientific exploration of feasibility of cell-based therapies.The underlying genetic mutation of Huntington's disease (HD) is a polyglutamine repeat in the N-terminal region of the huntingtin gene (3). This mutation results in brain pathology dominated by massive neuronal loss of the medium spiny projection neurons of the caudate and putamen (4). Recent studies of HD postmortem brain tissue show that the N-terminal region of the mutant huntingtin protein aggregates in nuclear inclusions in both cortical and striatal neurons (5-7). These aggregates may represent evidence of ongoing cellular pathology (5-7). Implanted fetal neural cells lacking the mutant HD gene may be able to replace dead or dysfunctional host neurons and reconstitute disrupted neuronal connections (8, 9).Physiological and anatomical evidence in animal st...