Jelena Krmpotić-Nemanić (1921–2008): Contributions to Human Neuroanatomy

Jelena Krmpoti}-Nemani} (1921–2008) was a world-famous anatomist, internationally distinguished otolaryngologist, a member of the Croatian Academy of Sciences & Arts and appreciated professor at the School of Medicine University of Zagreb. The founding influence in her scientific career came from her mentor Drago Perovi} who was a student of Ferdinand Hochstetter, the leading authority in the field of human developmental neuroanatomy and embryology. Such an influence was obviously important in early shaping of the research agenda of Jelena Krmpoti}-Nemani}, and it remains important in a long series of studies on developing human telencephalon initiated by Ivica Kostovi} and his collaborators – with an always present and active support of Jelena Krmpoti}-Nemani}. The aim of this mini review is to briefly describe her numerous contributions to the anatomy of the human peripheral and central nervous system

Functional neuroanatomy of nociception and pain

Pain is a complex sensory state based on the integration of a variety of nociceptive inputs processed centrally through many parallel and overlapping neural systems. The traditional anatomical concept implies that nociceptive information is dominantly used to generate and regulate perception of pain through one major sensory pathway. It becomes recognized that experiencing the affective component of the pain is at least as important as perception. Also, nociceptive information is strongly influencing brain centers for regulating homeostasis. So, understanding neuroanatomical organization of central processing of nociceptive information is of great clinical importance. There is an attempt to simplify this complex set of interacting networks to a core set of brain regions or a generalizable pain signature. Herewith we wish to give a short overview of recent advances by presenting principles about neuroanatomical organization for processing various aspects of nociceptive inputs

Primate-Specific Origins and Migration of Cortical GABAergic Neurons

Gamma-aminobutyric-acidergic (GABAergic) cells form a very heterogeneous population of neurons that play a crucial role in the coordination and integration of cortical functions. Their number and diversity increase through mammalian brain evolution. Does evolution use the same or different developmental rules to provide the increased population of cortical GABAergic neurons? In rodents, these neurons are not generated in the pallial proliferative zones as glutamatergic principal neurons. They are produced almost exclusively by the subpallial proliferative zones, the ganglionic eminence (GE) and migrate tangentially to reach their target cortical layers. The GE is organized in molecularly different subdomains that produce different subpopulations of cortical GABAergic neurons. In humans and non-human primates, in addition to the GE, cortical GABAergic neurons are also abundantly generated by the proliferative zones of the dorsal telencephalon. Neurogenesis in ventral and dorsal telencephalon occurs with distinct temporal profiles. These dorsal and ventral lineages give rise to different populations of GABAergic neurons. Early-generated GABAergic neurons originate from the GE and mostly migrate to the marginal zone and the subplate. Later-generated GABAergic neurons, originating from both proliferative sites, populate the cortical plate. Interestingly, the pool of GABAergic progenitors in dorsal telencephalon produces mainly calretinin neurons, a population known to be significantly increased and to display specific features in primates. We conclude that the development of cortical GABAergic neurons have exclusive features in primates that need to be considered in order to understand pathological mechanisms leading to some neurological and psychiatric diseases

Quantitative Analysis of Basal Dendritic Tree of Layer IIIc Pyramidal Neurons in Different Areas of Adult Human Frontal Cortex

Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca’s speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA’s. In addition, we analyzed each of these BA’s immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network

Distinct Origin of GABA-ergic Neurons in Forebrain of Man, Nonhuman Primates and Lower Mammals

In this mini-review we present recent data about origin of GABA-ergic (gama-aminobutyric acid) neurons in the mammalian forebrain, including the diencephalon and telencephalon. The interest in GABA-ergic neurons, which in cerebral cortex mostly correspond to local circuit neurons (interneurons), has increased in the past decade. Many studies have shown that in lower mammals all hippocampal and almost all neo-cortical GABA-ergic neurons are born in the specific region named ganglionic eminence, and not locally in proliferative layers all around telencephalic vesicle. The ganglionic eminence, that represents a region with thick proliferative-subventricular layer in the ventral (basal) part of telencephalon, was classically thought to give neurons to basal ganglia and septal nuclei, whereas proliferative layers of dorsal telencephalon give neurons to cerebral cortex including hippocampus. It was thought that neurons migrate from proliferative layer to their target region following a radial orientation. However, data in lower mammals showed that this is the case only for glutamatergic principal cells, i.e. projection neurons. GABA-ergic neurons use long distance tangentional migration, parallel to pial surface to reach, from ganglionic eminence, their targeting layer in the cerebral cortex. Especially intriguing, but frequently neglecting, several studies suggest that mammalian evolution might use different developmental rules to provide GABA-ergic neurons to an expending brain. In this review we focus on specific events underlying GABA-ergic neuron development in human and non-human primates. Disturbances of the GABAergic network are found in many neurological and psychiatric disorders, some of them might result from altered production or migration of these neurons during development. Therefore, it is crucial to understand human-specific mechanisms that regulate the development of GABA-ergic neurons

Axon morphology of rapid Golgistained pyramidal neurons in the prefrontal cortex in schizophrenia

Aim To analyze axon morphology on rapid Golgi impregnated pyramidal neurons in the dorsolateral prefrontal cortex in schizophrenia. Methods Postmortem brain tissue from five subjects diagnosed with schizophrenia and five control subjects without neuropathological findings was processed with the rapid Golgi method. Layer III and layer V pyramidal neurons from Brodmann area 9 were chosen in each brain for reconstruction with Neurolucida software. The axons and cell bodies of 136 neurons from subjects with schizophrenia and of 165 neurons from control subjects were traced. The data obtained by quantitative analysis were compared between the schizophrenia and control group with the t test. Results Axon impregnation length was consistently greater in the schizophrenia group. The axon main trunk length was significantly greater in the schizophrenia than in the control group (93.7±36.6 μm vs 49.8±9.9 μm, P=0.032). Furthermore, in the schizophrenia group more axons had visibly stained collaterals (14.7% vs 5.5%). Conclusion Axon rapid Golgi impregnation stops at the beginning of the myelin sheath. The increased axonal staining in the schizophrenia group could, therefore, be explained by reduced axon myelination. Such a decrease in axon myelination is in line with both the disconnection hypothesis and the two-hit model of schizophrenia as a neurodevelopmental disease. Our results support that the cortical circuitry disorganization in schizophrenia might be caused by functional alterations of two major classes of principal neurons due to altered oligodendrocyte development

Axon morphology of rapid Golgistained pyramidal neurons in the prefrontal cortex in schizophrenia

Aim To analyze axon morphology on rapid Golgi impregnated pyramidal neurons in the dorsolateral prefrontal cortex in schizophrenia. Methods Postmortem brain tissue from five subjects diagnosed with schizophrenia and five control subjects without neuropathological findings was processed with the rapid Golgi method. Layer III and layer V pyramidal neurons from Brodmann area 9 were chosen in each brain for reconstruction with Neurolucida software. The axons and cell bodies of 136 neurons from subjects with schizophrenia and of 165 neurons from control subjects were traced. The data obtained by quantitative analysis were compared between the schizophrenia and control group with the t test. Results Axon impregnation length was consistently greater in the schizophrenia group. The axon main trunk length was significantly greater in the schizophrenia than in the control group (93.7±36.6 μm vs 49.8±9.9 μm, P=0.032). Furthermore, in the schizophrenia group more axons had visibly stained collaterals (14.7% vs 5.5%). Conclusion Axon rapid Golgi impregnation stops at the beginning of the myelin sheath. The increased axonal staining in the schizophrenia group could, therefore, be explained by reduced axon myelination. Such a decrease in axon myelination is in line with both the disconnection hypothesis and the two-hit model of schizophrenia as a neurodevelopmental disease. Our results support that the cortical circuitry disorganization in schizophrenia might be caused by functional alterations of two major classes of principal neurons due to altered oligodendrocyte development

Quantitative Analysis of Basal Dendritic Tree of Layer IIIc Pyramidal Neurons in Different Areas of Adult Human Frontal Cortex

Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca’s speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA’s. In addition, we analyzed each of these BA’s immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network

Anatomija orofacijalne inervacije

The whole human body receives rich sensory innervation with only one exception and that is the brain tissue. The orofacial region is hence no exception. The head region consequently receives a rich network of sensory nerves making it special because the two types of sensory fibres, visceral and somatic overlap, especially in the pharynx. Also, different pain syndromes that affect this region are rather specific in comparison to their presentation in other body regions. With this review article we wanted to show the detailed anatomy of the peripheral sensory pathways, because of its importance in everyday body functions (eating, drinking, speech) as well as the importance it has in pathological conditions (pain syndromes), in diagnostics and regional analgesia and anaesthesia.Osjetna živčana vlakna prožimaju gotovo sva tkiva osim mozga ne izuzimajući tako ni orofacijalnu regiju. Područje glave je izrazito dobro osjetno inervirano, no ova je regija također posebna jer kao posljedica razvojnih događaja dolazi do preklapanja visceralne i somatske inervacije osobito u području ždrijela. Također, bolni sindromi koji zahvaćaju orofacijalnu regiju pokazuju neke specifičnosti koje ne nalazimo u drugim dijelovima tijela. Ovim preglednim člankom htjeli smo prikazati detaljnu anatomiju perifernih osjetnih putova zbog njihove važnost u svakodnevnim funkcijama za koje je odgovorno ovo područje (jedenje, pijenje, govorenje), ali isto tako i važnosti koju ima u patološkim slučajevima (bolni sindromi) te u dijagnostici i regionalnoj analgeziji i anesteziji