Reorganization of the 5-HT projections to the hippocampus

Frontiers in Cell and Developmental Biology, 2022

The modern thesis regarding the "structural plastic" properties of the brain, as reactions to injuries, to tissue damage, and to degenerative cell apoptosis, can hardly be seen as expendable in clinical neurology and its allied disciplines (including internal medicine, psychiatry, neurosurgery, radiology, etc.). It extends for instance to wider research areas of clinical physiology and neuropsychology which almost one hundred years ago had been described as a critically important area for the brain sciences and psychology alike. Yet the mounting evidence concerning the range of structural neuroplastic phenomena beyond the significant early 3 years of childhood has shown that there is a progressive building up and refining of neural circuits in adaptation to the surrounding environment. This review essay explores the history behind multiple biological phenomena that were studied and became theoretically connected with the thesis of brain regeneration from Santiago Ramón y Cajal's pioneering work since the 1890s to the beginning of the American "Decade of the Brain" in the 1990s. It particularly analyzes the neuroanatomical perspectives on the adaptive capacities of the Central Nervous System (CNS) as well as model-like phenomena in the Peripheral Nervous System (PNS), which were seen as displaying major central regenerative processes. Structural plastic phenomena have assumed large implications for the burgeoning field of regenerative or restorative medicine, while they also pose significant epistemological challenges for related experimental and theoretical research endeavors. Hereafter, early historical research precursors are examined, which investigated brain regeneration phenomena in non-vertebrates at the beginning of the 20th century, such as in light microscopic studies and later in electron microscopic findings that substantiated the presence of structural neuroplastic phenomena in higher cortical substrates. Furthermore, experimental physiological research in hippocampal in vivo models of regeneration further confirmed and corroborated clinical physiological views, according to which "structural plasticity" could be interpreted as a positive regenerative CNS response to brain damage and degeneration. Yet the underlying neuroanatomical mechanisms remained to be established and the respective pathway effects were only conveyed through the discovery of neural stem cells in in adult mammalian brains in the early 1990s. Experimental results have since emphasized the genuine existence of adult neurogenesis phenomena in the CNS. The focus in this essay will be laid here on questions of the structure and function of scientific concepts, the development of research schools among biomedical investigators, as well as the impact of new data and phenomena through innovative methodologies and laboratory instruments in the neuroscientific endeavors of the 20th century.

In order to study the morphological substrate of possible thalamic influence on the cells of origin and area of termination of the projection from the entorhinal cortex to the hippocampal formation, we examined the pathways, terminal distribution, and ultrastructure of the innervation of the hippocampal formation and parahippocampal region by the nucleus reuniens of the thalamus (NRT). We employed anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L). Injections of PHA-L in the NRT produce fiber and terminal labeling in the stratum lacunosum-moleculare of field CAI of the hippocampus, the molecular layer of the subiculum, layers I and III/IV of the dorsal subdivision of the lateral entorhinal area (DLEA), and layers I and 111-VI of the ventral lateral (VLEA) and medial (MEA) divisions of the entorhinal cortex. Terminal labeling is most dense in the stratum lacunosum-moleculare of field CA1, the molecular layer of the ventral part of the subiculum, MEA, and layer I of the perirhinal cortex. In layer I of the caudal part of DLEA and in MEA, terminal labeling is present in clusters. Injections in the rostral half of the NRT produce the same distribution in the hippocampal region as those in the caudal half of the NRT, although the projections from the rostral half of the NRT are much stronger. A topographical organization is present in the projections from the head of the NRT, so that the dorsal part projects predominantly to dorsal parts of field CA1 and the subiculum and to lateral parts of the entorhinal cortex, whereas the ventral part projects in greatest volume to ventral parts of field CA1 and the subiculum and to medial parts of the entorhinal cortex.

Neural Regeneration Research, 2016

The dynamics of adult neurogenesis in human hippocampus Historical Perspective The inability of the adult brain to generate neurons throughout life was a central dogma in neurobiology. For decades, there was little or no progress for the field. The adult brain was thought to be hard wired and incapable of generating new neurons. A famous neurobiologist, Santiago Ramon y Cajal in 1913 stated "In the adult centres, the nerve paths are something fixed, ended and immutable. Everything may die, nothing may be regenerated, " (Ramon y Cajal, 1928). And this was in part a reason for slow progress for decades for the field. The complexity of the neural networks in an adult brain affirmed this view, hence new neurons were assumed if added would destabilize the neuronal network (Jessberger and Gage, 2014) as such, it was impossible to integrate the new cells. Incorporation of new neurons was thought that it would destabilize

Annals of the New York Academy of Sciences, 1993

Throughout life, neuronal circuitry is continually changing and undergoing reorganization. At one level, the population of neurons changes while at another level, neuronal connectivity changes. Early in life as a normal part of the development of the brain, neurons are overproduced and pruned back as neuronal circuitry is Once mature, select systems in the central nervous system (CNS) continue to exhibit slow neuronal loss, perhaps as a normal process or due to the accumulation of insults to the brain. The rate of neuronal loss increases as the aging process continues, often compounded by the onset of conditions such as e p i l e p ~y ~. ~ and neurodegenerative diseases such as Alzheimer's d i ~e a s e . ~ Along with continuous neuronal cell loss, the brain has a remarkable capacity for the continuous reorganization and regrowth of connections. Sprouting of axons and dendrites from surviving neurons is elicited in response to neuronal loss throughout life.6 These processes are thought to represent compensatory mechanisms, a natural attempt of the CNS to repair or rebuild damaged neuronal circuitry. With subtler loss, reactive synaptogenesis may help maintain function and trophic interactions, whereas after extensive damage, regrowth may contribute to recovery (functional plasticity) or may hinder recovery (dysfunctional plasticity). A major challenge in modern neuroscience, therefore, is to characterize the sprouting response and its relation to behavioral recovery in order to aid in the identification of promising targets and strategies for therapeutic intervention.

Acta Neuropsychologica

The main aim of the paper is to show that many previously forgotten discoveries within the field of neuroscience own their rediscovery and renaissance to the refinement of tools provided by the technological advances. Most spectacular is the advancement of brain imaging techniques, which provide hard data that support for evidence for previously neglected presumptions and ideas. Neuroplasticity is an example of such a long ignored historical discovery. One reason for that neglect is that it stood in contradiction to beliefs and theories prevailing at the first half of the twenties century. The idea of neuronal plasticity is not disputed any longer since it has found confirmation not only in a dramatic development of neuroimaging but also in the advancement of neurobiology. Most authors concentrate upon neuronal plasticity, recent studies, however, have produced a wealth of information regarding neurogenesis, in which astrocytes have proved to play a significant role. The significanc...

Bratislavské lekárske listy, 2006

The complex structures in the cerebral hemispheres is included under one term, the limbic system. Our conception of this system and its special functions rises from the comparative neuroanatomical and neurophysiological studies. The components of the limbic system are the hippocampus, gyrus parahippocampalis, gyrus dentatus, gyrus cinguli, corpus amygdaloideum, nuclei anteriores thalami, hypothalamus and gyrus paraterminalis Because of its unique macroscopic and microscopic structure, the hippocampus is a conspicuous part of the limbic system. During phylogenetic development, the hippocampus developed from a simple cortical plate in amphibians into complex three-dimensional convoluted structure in mammals. In the last few decades, structures of the limbic system were extensively studied. Attention was directed to the physiological functions and pathological changes of the hippocampus. Experimental studies proved that the hippocampus has a very important role in the process of learni...

AJNR. American journal of neuroradiology

Brain plasticity includes the enormous changes of normal prenatal and postnatal development, responses to normal experience such as the springtime reemergence of bird song, and responses to injury. This broad view of plasticity brings together the large and growing fields of developmental neuroscience, learning and memory, and responses to injury. Such a synthetic view is essential now that these fields are being elucidated at cellular and molecular levels. The major stages of normal brain development are very similar to those of plasticity induced by experience. Particular cellular or subcellular de,.. tails are similar, depending on the specific case. Importantly, these common steps are the very ones we most need to understand if the outcome of brain and spinal cord injury is to be improved. Knowledge of brain plasticity will be the basis for innovative treatmenf of such injuries. Relevant mechanisms reviewed here include chemical stimulation of receptors, regulation of gene expression in surviving cells, gene introduction by viral or cellular vectors, cell-cell interactions such as guidance of axons, and replacing neurons lost by injury. Increasing knowledge of plasticity and its application to therapy offers promising approaches for improving the outcome of cerebral and spinal injury, making optimism unavoidable.

International Journal of Indian Psychology, 2016

The brain is the most important organ of human body. It is dynamic in terms of functional and structural aspects. Each human function is determined by brain. It was thought in the beginning that brain or its tissues do not regenerate once they are damaged. The recent research in neurosciences has shown that brain tissues have the ability to regenerate themselves. This phenomenon is known as neuronal plasticity. There have been multiple mechanisms which explain this phenomenon. Post injury experiences, neurochemical and neurophysiological aspects are some of the underlying mechanisms. The current paper attempts to explain the neurophysiological aspects of neuroplasticity. It has significant therapeutic implications.

Neural Development, 2013

Background: Although the brains of lower vertebrates are known to exhibit somewhat limited regeneration after incisional or stab wounds, the Urodele brain exhibits extensive regeneration after massive tissue removal. Discovering whether and how neural progenitor cells that reside in the ventricular zones of Urodeles proliferate to mediate tissue repair in response to injury may produce novel leads for regenerative strategies. Here we show that endogenous neural progenitor cells resident to the ventricular zone of Urodeles spontaneously proliferate, producing progeny that migrate throughout the telencephalon before terminally differentiating into neurons. These progenitor cells appear to be responsible for telencephalon regeneration after tissue removal and their activity may be up-regulated by injury through an olfactory cue. Results: There is extensive proliferation of endogenous neural progenitor cells throughout the ventricular zone of the adult axolotl brain. The highest levels are observed in the telencephalon, especially the dorsolateral aspect, and cerebellum. Lower levels are observed in the mesencephalon and rhombencephalon. New cells produced in the ventricular zone migrate laterally, dorsally and ventrally into the surrounding neuronal layer. After migrating from the ventricular zone, the new cells primarily express markers of neuronal differentiative fates. Large-scale telencephalic tissue removal stimulates progenitor cell proliferation in the ventricular zone of the damaged region, followed by proliferation in the tissue that surrounds the healing edges of the wound until the telencephalon has completed regeneration. The proliferative stimulus appears to reside in the olfactory system, because telencephalic regeneration does not occur in the brains of olfactory bulbectomized animals in which the damaged neural tissue simply heals over. Conclusion: There is a continual generation of neuronal cells from neural progenitor cells located within the ventricular zone of the axolotl brain. Variable rates of proliferation were detected across brain regions. These neural progenitor cells appear to mediate telencephalic tissue regeneration through an injury-induced olfactory cue. Identification of this cue is our future goal.