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  1. Article ; Online: Neuroanatomy of autism: what is the role of the cerebellum?

    Baizer, Joan S

    Cerebral cortex (New York, N.Y. : 1991)

    2024  Volume 34, Issue 13, Page(s) 94–103

    Abstract: Autism (or autism spectrum disorder) was initially defined as a psychiatric disorder, with the likely cause maternal behavior (the very destructive "refrigerator mother" theory). It took several decades for research into brain mechanisms to become ... ...

    Abstract Autism (or autism spectrum disorder) was initially defined as a psychiatric disorder, with the likely cause maternal behavior (the very destructive "refrigerator mother" theory). It took several decades for research into brain mechanisms to become established. Both neuropathological and imaging studies found differences in the cerebellum in autism spectrum disorder, the most widely documented being a decreased density of Purkinje cells in the cerebellar cortex. The popular interpretation of these results is that cerebellar neuropathology is a critical cause of autism spectrum disorder. We challenge that view by arguing that if fewer Purkinje cells are critical for autism spectrum disorder, then any condition that causes the loss of Purkinje cells should also cause autism spectrum disorder. We will review data on damage to the cerebellum from cerebellar lesions, tumors, and several syndromes (Joubert syndrome, Fragile X, and tuberous sclerosis). Collectively, these studies raise the question of whether the cerebellum really has a role in autism spectrum disorder. Autism spectrum disorder is now recognized as a genetically caused developmental disorder. A better understanding of the genes that underlie the differences in brain development that result in autism spectrum disorder is likely to show that these genes affect the development of the cerebellum in parallel with the development of the structures that do underlie autism spectrum disorder.
    MeSH term(s) Humans ; Cerebellum/pathology ; Autism Spectrum Disorder/pathology ; Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/physiopathology ; Autism Spectrum Disorder/diagnostic imaging ; Animals ; Autistic Disorder/pathology ; Autistic Disorder/genetics ; Autistic Disorder/physiopathology ; Purkinje Cells/pathology
    Language English
    Publishing date 2024-05-02
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1077450-6
    ISSN 1460-2199 ; 1047-3211
    ISSN (online) 1460-2199
    ISSN 1047-3211
    DOI 10.1093/cercor/bhae050
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  2. Article: Functional and Neuropathological Evidence for a Role of the Brainstem in Autism.

    Baizer, Joan S

    Frontiers in integrative neuroscience

    2021  Volume 15, Page(s) 748977

    Abstract: The brainstem includes many nuclei and fiber tracts that mediate a wide range of functions. Data from two parallel approaches to the study of autistic spectrum disorder (ASD) implicate many brainstem structures. The first approach is to identify the ... ...

    Abstract The brainstem includes many nuclei and fiber tracts that mediate a wide range of functions. Data from two parallel approaches to the study of autistic spectrum disorder (ASD) implicate many brainstem structures. The first approach is to identify the functions affected in ASD and then trace the neural systems mediating those functions. While not included as core symptoms, three areas of function are frequently impaired in ASD: (1) Motor control both of the limbs and body and the control of eye movements; (2) Sensory information processing in vestibular and auditory systems; (3) Control of affect. There are critical brainstem nuclei mediating each of those functions. There are many nuclei critical for eye movement control including the superior colliculus. Vestibular information is first processed in the four nuclei of the vestibular nuclear complex. Auditory information is relayed to the dorsal and ventral cochlear nuclei and subsequently processed in multiple other brainstem nuclei. Critical structures in affect regulation are the brainstem sources of serotonin and norepinephrine, the raphe nuclei and the locus ceruleus. The second approach is the analysis of abnormalities from direct study of ASD brains. The structure most commonly identified as abnormal in neuropathological studies is the cerebellum. It is classically a major component of the motor system, critical for coordination. It has also been implicated in cognitive and language functions, among the core symptoms of ASD. This structure works very closely with the cerebral cortex; the cortex and the cerebellum show parallel enlargement over evolution. The cerebellum receives input from cortex via relays in the pontine nuclei. In addition, climbing fiber input to cerebellum comes from the inferior olive of the medulla. Mossy fiber input comes from the arcuate nucleus of the medulla as well as the pontine nuclei. The cerebellum projects to several brainstem nuclei including the vestibular nuclear complex and the red nucleus. There are thus multiple brainstem nuclei distributed at all levels of the brainstem, medulla, pons, and midbrain, that participate in functions affected in ASD. There is direct evidence that the cerebellum may be abnormal in ASD. The evidence strongly indicates that analysis of these structures could add to our understanding of the neural basis of ASD.
    Language English
    Publishing date 2021-10-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452962-X
    ISSN 1662-5145
    ISSN 1662-5145
    DOI 10.3389/fnint.2021.748977
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  3. Article: Comparative analysis of four nuclei in the human brainstem: Individual differences, left-right asymmetry, species differences.

    Baizer, Joan S / Witelson, Sandra F

    Frontiers in neuroanatomy

    2023  Volume 17, Page(s) 1069210

    Abstract: Introduction: It is commonly thought that while the organization of the cerebral cortex changes dramatically over evolution, the organization of the brainstem is conserved across species. It is further assumed that, as in other species, brainstem ... ...

    Abstract Introduction: It is commonly thought that while the organization of the cerebral cortex changes dramatically over evolution, the organization of the brainstem is conserved across species. It is further assumed that, as in other species, brainstem organization is similar from one human to the next. We will review our data on four human brainstem nuclei that suggest that both ideas may need modification.
    Methods: We have studied the neuroanatomical and neurochemical organization of the nucleus paramedianus dorsalis (PMD), the principal nucleus of the inferior olive (IOpr), the arcuate nucleus of the medulla (Arc) and the dorsal cochlear nucleus (DC). We compared these human brainstem nuclei to nuclei in other mammals including chimpanzees, monkeys, cats and rodents. We studied human cases from the Witelson Normal Brain collection using Nissl and immunostained sections, and examined archival Nissl and immunostained sections from other species.
    Results: We found significant individual variability in the size and shape of brainstem structures among humans. There is left-right asymmetry in the size and appearance of nuclei, dramatically so in the IOpr and Arc. In humans there are nuclei, e.g., the PMD and the Arc, not seen in several other species. In addition, there are brainstem structures that are conserved across species but show major expansion in humans, e.g., the IOpr. Finally, there are nuclei, e.g. the DC, that show major differences in structure among species.
    Discussion: Overall, the results suggest several principles of human brainstem organization that distinguish humans from other species. Studying the functional correlates of, and the genetic contributions to, these brainstem characteristics are important future research directions.
    Language English
    Publishing date 2023-02-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452969-2
    ISSN 1662-5129
    ISSN 1662-5129
    DOI 10.3389/fnana.2023.1069210
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  4. Article: Glycine is a transmitter in the human and chimpanzee cochlear nuclei.

    Baizer, Joan S / Sherwood, Chet C / Hof, Patrick R / Baker, James F / Witelson, Sandra F

    Frontiers in neuroanatomy

    2024  Volume 18, Page(s) 1331230

    Abstract: Introduction: Auditory information is relayed from the cochlea via the eighth cranial nerve to the dorsal and ventral cochlear nuclei (DCN, VCN). The organization, neurochemistry and circuitry of the cochlear nuclei (CN) have been studied in many ... ...

    Abstract Introduction: Auditory information is relayed from the cochlea via the eighth cranial nerve to the dorsal and ventral cochlear nuclei (DCN, VCN). The organization, neurochemistry and circuitry of the cochlear nuclei (CN) have been studied in many species. It is well-established that glycine is an inhibitory transmitter in the CN of rodents and cats, with glycinergic cells in the DCN and VCN. There are, however, major differences in the laminar and cellular organization of the DCN between humans (and other primates) and rodents and cats. We therefore asked whether there might also be differences in glycinergic neurotransmission in the CN.
    Methods: We studied brainstem sections from humans, chimpanzees, and cats. We used antibodies to glycine receptors (GLYR) to identify neurons receiving glycinergic input, and antibodies to the neuronal glycine transporter (GLYT2) to immunolabel glycinergic axons and terminals. We also examined archival sections immunostained for calretinin (CR) and nonphosphorylated neurofilament protein (NPNFP) to try to locate the octopus cell area (OCA), a region in the VCN that rodents has minimal glycinergic input.
    Results: In humans and chimpanzees we found widespread immunolabel for glycine receptors in DCN and in the posterior (PVCN) and anterior (AVCN) divisions of the VCN. We found a parallel distribution of GLYT2-immunolabeled fibers and puncta. The data also suggest that, as in rodents, a region containing octopus cells in cats, humans and chimpanzees has little glycinergic input.
    Discussion: Our results show that glycine is a major transmitter in the human and chimpanzee CN, despite the species differences in DCN organization. The sources of the glycinergic input to the CN in humans and chimpanzees are not known.
    Language English
    Publishing date 2024-02-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452969-2
    ISSN 1662-5129
    ISSN 1662-5129
    DOI 10.3389/fnana.2024.1331230
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  5. Article ; Online: Characterization of the superior olivary complex of chimpanzees (Pan troglodytes) in comparison to humans.

    Alhelo, Hasan / Dogiparthi, Jaswanthi / Baizer, Joan S / Hof, Patrick R / Sherwood, Chet C / Kulesza, Randy

    Hearing research

    2023  Volume 430, Page(s) 108698

    Abstract: The superior olivary complex (SOC) is a collection of nuclei in the hindbrain of mammals with numerous roles in hearing, including localization of sound sources in the environment, encoding temporal and spectral elements of sound, and descending ... ...

    Abstract The superior olivary complex (SOC) is a collection of nuclei in the hindbrain of mammals with numerous roles in hearing, including localization of sound sources in the environment, encoding temporal and spectral elements of sound, and descending modulation of the cochlea. While there have been several investigations of the SOC in primates, there are discrepancies in the descriptions of nuclear borders and even the presence of certain cell groups among studies and species. Herein, we aimed to clarify some of these issues by characterizing the SOC from chimpanzees using Nissl staining, quantitative morphometry and immunohistochemistry. We found the medial superior olive (MSO) to be the largest of the SOC nuclei and the arrangement of its neurons and peri-MSO to be very similar to humans. Additionally, we found neurons in the medial nucleus of the trapezoid body (MNTB) to be immunopositive for the calcium binding protein calbindin. Further, most neurons in the MNTB, and some neurons in the lateral nucleus of the trapezoid body were associated with large, calretinin-immunoreactive calyx terminals. Together, these findings indicate the organization of the SOC of chimpanzees is organized very similar to the SOC in humans and suggests modifications to this region among species consistent with differences in head/body size, restricted hearing range and sensitivity to low frequency sounds.
    MeSH term(s) Animals ; Humans ; Auditory Pathways/physiology ; Neurons/physiology ; Olivary Nucleus/physiology ; Pan troglodytes ; Superior Olivary Complex/physiology
    Language English
    Publishing date 2023-01-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 282629-x
    ISSN 1878-5891 ; 0378-5955
    ISSN (online) 1878-5891
    ISSN 0378-5955
    DOI 10.1016/j.heares.2023.108698
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  6. Article ; Online: Individual variability in the size and organization of the human arcuate nucleus of the medulla.

    Baizer, Joan S / Webster, Charles J / Witelson, Sandra F

    Brain structure & function

    2021  Volume 227, Issue 1, Page(s) 159–176

    Abstract: The arcuate nucleus (Arc) of the medulla is found in almost all human brains and in a small percentage of chimpanzee brains. It is absent in the brains of other mammalian species including mice, rats, cats, and macaque monkeys. The Arc is classically ... ...

    Abstract The arcuate nucleus (Arc) of the medulla is found in almost all human brains and in a small percentage of chimpanzee brains. It is absent in the brains of other mammalian species including mice, rats, cats, and macaque monkeys. The Arc is classically considered a precerebellar relay nucleus, receiving input from the cerebral cortex and projecting to the cerebellum via the inferior cerebellar peduncle. However, several studies have found aplasia of the Arc in babies who died of SIDS (Sudden Infant Death Syndrome), and it was suggested that the Arc is the locus of chemosensory neurons critical for brainstem control of respiration. Aplasia of the Arc, however, has also been reported in adults, suggesting that it is not critical for survival. We have examined the Arc in closely spaced Nissl-stained sections in thirteen adult human cases to acquire a better understanding of the degree of variability of its size and location in adults. We have also examined immunostained sections to look for neurochemical compartments in this nucleus. Caudally, neurons of the Arc are ventrolateral to the pyramidal tracts (py); rostrally, they are ventro-medial to the py and extend up along the midline. In some cases, the Arc is discontinuous, with a gap between sections with the ventrolaterally located and the ventromedially located neurons. In all cases, there is some degree of left-right asymmetry in Arc position, size, and shape at all rostro-caudal levels. Somata of neurons in the Arc express calretinin (CR), neuronal nitric oxide synthase (nNOS), and nonphosphorylated neurofilament protein (NPNFP). Calbindin (CB) is expressed in puncta whereas there is no expression of parvalbumin (PV) in somata or puncta. There is also immunostaining for GAD and GABA receptors suggesting inhibitory input to Arc neurons. These properties were consistent among cases. Our data show differences in location of caudal and rostral Arc neurons and considerable variability among cases in the size and shape of the Arc. The variability in size suggests that "hypoplasia" of the Arc is difficult to define. The discontinuity of the Arc in many cases suggests that establishing aplasia of the Arc requires examination of many closely spaced sections through the brainstem.
    MeSH term(s) Arcuate Nucleus of Hypothalamus/metabolism ; Brain Stem/metabolism ; Calbindins ; Humans ; Medulla Oblongata/metabolism ; Neurofilament Proteins/metabolism
    Chemical Substances Calbindins ; Neurofilament Proteins
    Language English
    Publishing date 2021-10-06
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2273162-3
    ISSN 1863-2661 ; 1863-2653
    ISSN (online) 1863-2661
    ISSN 1863-2653
    DOI 10.1007/s00429-021-02396-4
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  7. Article: Unique features of the human brainstem and cerebellum.

    Baizer, Joan S

    Frontiers in human neuroscience

    2014  Volume 8, Page(s) 202

    Abstract: The cerebral cortex is greatly expanded in the human brain. There is a parallel expansion of the cerebellum, which is interconnected with the cerebral cortex. We have asked if there are accompanying changes in the organization of pre-cerebellar brainstem ...

    Abstract The cerebral cortex is greatly expanded in the human brain. There is a parallel expansion of the cerebellum, which is interconnected with the cerebral cortex. We have asked if there are accompanying changes in the organization of pre-cerebellar brainstem structures. We have examined the cytoarchitectonic and neurochemical organization of the human medulla and pons. We studied human cases from the Witelson Normal Brain Collection, analyzing Nissl sections and sections processed for immunohistochemistry for multiple markers including the calcium-binding proteins calbindin, calretinin, and parvalbumin, non-phosphorylated neurofilament protein, and the synthetic enzyme for nitric oxide, nitric oxide synthase. We have also compared the neurochemical organization of the human brainstem to that of several other species including the chimpanzee, macaque and squirrel monkey, cat, and rodent, again using Nissl staining and immunohistochemistry. We found that there are major differences in the human brainstem, ranging from relatively subtle differences in the neurochemical organization of structures found in each of the species studied to the emergence of altogether new structures in the human brainstem. Two aspects of human cortical organization, individual differences and left-right asymmetry, are also seen in the brainstem (principal nucleus of the inferior olive) and the cerebellum (the dentate nucleus). We suggest that uniquely human motor and cognitive abilities derive from changes at all levels of the central nervous system, including the cerebellum and brainstem, and not just the cerebral cortex.
    Language English
    Publishing date 2014-04-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2425477-0
    ISSN 1662-5161
    ISSN 1662-5161
    DOI 10.3389/fnhum.2014.00202
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  8. Article ; Online: Introduction to the JCN Special Issue on the Claustrum.

    Baizer, Joan S / Reser, David

    The Journal of comparative neurology

    2017  Volume 525, Issue 6, Page(s) 1315–1316

    MeSH term(s) Animals ; Basal Ganglia/anatomy & histology ; Phylogeny
    Language English
    Publishing date 2017-02-16
    Publishing country United States
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 3086-7
    ISSN 1096-9861 ; 0021-9967 ; 0092-7317
    ISSN (online) 1096-9861
    ISSN 0021-9967 ; 0092-7317
    DOI 10.1002/cne.24182
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  9. Article ; Online: The Claustrum in the Squirrel Monkey.

    Baizer, Joan S / Webster, Charles J / Baker, James F

    Anatomical record (Hoboken, N.J. : 2007)

    2019  Volume 303, Issue 5, Page(s) 1439–1454

    Abstract: The claustrum (CLA) is a subcortical structure that is reciprocally and topographically connected with the cerebral cortex. The complexity of the cerebral cortex varies dramatically across mammals, raising the question of whether there might also be ... ...

    Abstract The claustrum (CLA) is a subcortical structure that is reciprocally and topographically connected with the cerebral cortex. The complexity of the cerebral cortex varies dramatically across mammals, raising the question of whether there might also be differences in CLA organization, circuitry, and function. Species variations in the shape of the CLA are well documented. Studies in multiple species have identified subsets of neurochemically distinct interneurons; some data suggest species variations in the nature, distribution, and numbers of different neurochemically identified neuronal types. We have studied the CLA in a smooth-brained primate, the squirrel monkey, using Nissl-stained sections and immunohistochemistry. We found that the shape of the CLA is different from that in other primates. We found several different neurochemically defined populations of neurons equally distributed throughout the CLA. Immunoreactivity to GAD
    MeSH term(s) Amino Acid Transport System X-AG/metabolism ; Animals ; Calbindins/metabolism ; Claustrum/metabolism ; GABAergic Neurons/metabolism ; Immunohistochemistry ; Interneurons/metabolism ; Neurons/metabolism ; Saimiri/metabolism
    Chemical Substances Amino Acid Transport System X-AG ; Calbindins
    Language English
    Publishing date 2019-10-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2269667-2
    ISSN 1932-8494 ; 1932-8486
    ISSN (online) 1932-8494
    ISSN 1932-8486
    DOI 10.1002/ar.24253
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  10. Article ; Online: Nonphosphorylated neurofilament protein is expressed by scattered neurons in the vestibular and precerebellar brainstem.

    Baizer, Joan S

    Brain research

    2009  Volume 1298, Page(s) 46–56

    Abstract: Vestibular information is essential for the control of posture, balance, and eye movements. The vestibular nerve projects to the four nuclei of the vestibular nuclear complex (VNC), as well as to several additional brainstem nuclei and the cerebellum. We ...

    Abstract Vestibular information is essential for the control of posture, balance, and eye movements. The vestibular nerve projects to the four nuclei of the vestibular nuclear complex (VNC), as well as to several additional brainstem nuclei and the cerebellum. We have found that expression of the calcium-binding proteins calretinin (CR) and calbindin (CB), and the synthetic enzyme for nitric oxide synthase (nNOS) define subdivisions of the medial vestibular nucleus (MVe) and the nucleus prepositus (PrH), in cat, monkey, and human. We have asked if the pattern of expression of nonphosphorylated neurofilament protein (NPNFP) might define additional subdivisions of these or other nuclei that participate in vestibular function. We studied the distribution of cells immunoreactive to NPNFP in the brainstems of 5 cats and one squirrel monkey. Labeled cells were scattered throughout the four nuclei of the VNC, as well as in PrH, the reticular formation (RF) and the external cuneate nucleus. We used double-label immunofluorescence to visualize the distribution of these cells relative to other neurochemically defined subdivisions. NPNFP cells were excluded from the CR and CB regions of the MVe. In PrH, NPNFP and nNOS were not colocalized. Cells in the lateral vestibular nucleus and RF colocalized NPNFP and a marker for glutamatergic neurons. We also found that the cholinergic cells and axons of cranial nerve nuclei 3, 4, 6, 7,10 and 12 colocalize NPNFP. The data suggest that NPNFP is expressed by a subset of glutamatergic projection neurons of the vestibular brainstem. NPNFP may be a marker for those cells that are especially vulnerable to the effects of normal aging, neurological disease or disruption of sensory input.
    MeSH term(s) Animals ; Cats ; Choline O-Acetyltransferase/metabolism ; Cranial Nerves/metabolism ; Fluorescent Antibody Technique ; Glutamic Acid/metabolism ; Medulla Oblongata/metabolism ; Neurofilament Proteins/metabolism ; Neurons/metabolism ; Reticular Formation/metabolism ; Saimiri ; Vestibular Nuclei/metabolism
    Chemical Substances Neurofilament Proteins ; Glutamic Acid (3KX376GY7L) ; Choline O-Acetyltransferase (EC 2.3.1.6)
    Language English
    Publishing date 2009-09-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2009.08.073
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