-
Current Opinion in Neurobiology Oct 2011This review focuses on recent advances in our understanding of how neural divergence and convergence give rise to complex encoding properties of retinal ganglion cells.... (Review)
Review
This review focuses on recent advances in our understanding of how neural divergence and convergence give rise to complex encoding properties of retinal ganglion cells. We describe the apparent mismatch between the number of cone bipolar cell types, and the diversity of excitatory input to retinal ganglion cells, and outline two possible solutions. One proposal is for diversity in the excitatory pathways to be generated within axon terminals of cone bipolar cells, and the second invokes narrow-field glycinergic amacrine cells that can apparently act like bipolar cells by providing excitatory drive to ganglion cells. Finally we highlight two advances in technique that promise to provide future insights; automation of electron microscope data collection and analysis, and the use of the ideal observer to quantitatively compare neural performance at all levels.
Topics: Animals; Humans; Models, Biological; Neurons; Photic Stimulation; Retina; Visual Pathways
PubMed: 21821411
DOI: 10.1016/j.conb.2011.07.001 -
Bipolar Disorders Mar 2019This limited review examines the role of the reticular activating system (RAS), especially the pedunculopontine nucleus (PPN), one site of origin of bottom-up gamma, in... (Review)
Review
OBJECTIVES
This limited review examines the role of the reticular activating system (RAS), especially the pedunculopontine nucleus (PPN), one site of origin of bottom-up gamma, in the symptoms of bipolar disorder (BD).
METHODS
The expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of BD patients is increased. It has recently been found that all PPN neurons manifest intrinsic membrane beta/gamma frequency oscillations mediated by high threshold calcium channels, suggesting that it is one source of bottom-up gamma. This review specifically addresses the involvement of these channels in the manifestation of BD.
RESULTS
Excess NCS-1 was found to dampen gamma band oscillations in PPN neurons. Lithium, a first line treatment for BD, was found to decrease the effects of NCS-1 on gamma band oscillations in PPN neurons. Moreover, gamma band oscillations appear to epigenetically modulate gene transcription in PPN neurons, providing a new direction for research in BD.
CONCLUSIONS
This is an area needing much additional research, especially since the dysregulation of calcium channels may help explain many of the disorders of arousal in, elicit unwanted neuroepigenetic modulation in, and point to novel therapeutic avenues for, BD.
Topics: Animals; Bipolar Disorder; Calcium Channels; Epigenesis, Genetic; Gamma Rhythm; Humans; Neuronal Calcium-Sensor Proteins; Neurons; Neuropeptides; Pedunculopontine Tegmental Nucleus
PubMed: 30506611
DOI: 10.1111/bdi.12735 -
The Journal of Comparative Neurology Jul 2022Bipolar cells convey signals from photoreceptors in the outer retina to amacrine and ganglion cells in the inner retina. In mammals, there are typically 10-15 types of...
Bipolar cells convey signals from photoreceptors in the outer retina to amacrine and ganglion cells in the inner retina. In mammals, there are typically 10-15 types of cone bipolar cells and one type of rod bipolar cell. Different types of cone bipolar cells are thought to code and transmit different features of a complex visual stimulus, thereby generating parallel channels that uniquely filter and transform the photoreceptor outputs. Differential synaptic connectivity and expression of ligand- and voltage-gated ion channels are thought to be important mechanisms for processing and filtering visual signals. Whereas the biophysical basis for such mechanisms has been investigated more extensively in rat retina, there is a lack of quantitative morphological data necessary for advancing the structure-function correlation in this species, as recent connectomics investigations have focused on mouse retina. Here, we performed whole-cell recordings from cone and rod bipolar cells in rat retinal slices, filled the cells with fluorescent dyes, and acquired image stacks by multiphoton excitation microscopy. Following deconvolution, we performed digital reconstruction and morphometric analysis of 25 cone and 14 rod bipolar cells. Compared to previous descriptions, the extent and complexity of branching of the axon terminal was surprisingly high. By precisely quantifying the level of stratification of the axon terminals in the inner plexiform layer, we have generated a reference system for reliable classification of individual cells in future studies focused on correlating physiological and morphological properties. The implemented workflow can be extended to the development of morphologically realistic compartmental models for these neurons.
Topics: Animals; Axons; Dendrites; Mammals; Mice; Rats; Retina; Retinal Bipolar Cells; Retinal Cone Photoreceptor Cells
PubMed: 35152437
DOI: 10.1002/cne.25308 -
Cells Jun 2019Neuronal migration is essential for the orchestration of brain development and involves several contiguous steps: interkinetic nuclear movement (INM), multipolar-bipolar... (Review)
Review
Neuronal migration is essential for the orchestration of brain development and involves several contiguous steps: interkinetic nuclear movement (INM), multipolar-bipolar transition, locomotion, and translocation. Growing evidence suggests that Rho GTPases, including RhoA, Rac, Cdc42, and the atypical Rnd members, play critical roles in neuronal migration by regulating both actin and microtubule cytoskeletal components. This review focuses on the spatiotemporal-specific regulation of Rho GTPases as well as their regulators and effectors in distinct steps during the neuronal migration process. Their roles in bridging extracellular signals and cytoskeletal dynamics to provide optimal structural support to the migrating neurons will also be discussed.
Topics: Adherens Junctions; Animals; Cell Movement; Ependymoglial Cells; Humans; Neurogenesis; Neurons; cdc42 GTP-Binding Protein; rho GTP-Binding Proteins
PubMed: 31185627
DOI: 10.3390/cells8060568 -
The Journal of Neuroscience : the... Mar 2022Dendrite and axon arbor sizes are critical to neuronal function and vary widely between different neuron types. The relative dendrite and axon sizes of synaptic partners...
Dendrite and axon arbor sizes are critical to neuronal function and vary widely between different neuron types. The relative dendrite and axon sizes of synaptic partners control signal convergence and divergence in neural circuits. The developmental mechanisms that determine cell-type-specific dendrite and axon size and match synaptic partners' arbor territories remain obscure. Here, we discover that retinal horizontal cells express the leucine-rich repeat domain cell adhesion molecule AMIGO1. Horizontal cells provide pathway-specific feedback to photoreceptors-horizontal cell axons to rods and horizontal cell dendrites to cones. AMIGO1 selectively expands the size of horizontal cell axons. When is deleted in all or individual horizontal cells of either sex, their axon arbors shrink. By contrast, horizontal cell dendrites and synapse formation of horizontal cell axons and dendrites are unaffected by AMIGO1 removal. The dendrites of rod bipolar cells, which do not express AMIGO1, shrink in parallel with horizontal cell axons in () mice. This territory matching maintains the function of the rod bipolar pathway, preserving bipolar cell responses and retinal output signals in mice. We previously identified AMIGO2 as a scaling factor that constrains retinal neurite arbors. Our current results identify AMIGO1 as a scaling factor that expands retinal neurite arbors and reveal territory matching as a novel homeostatic mechanism. Territory matching interacts with other homeostatic mechanisms to stabilize the development of the rod bipolar pathway, which mediates vision near the threshold. Neurons send and receive signals through branched axonal and dendritic arbors. The size of these arbors is critical to the function of a neuron. Axons and dendrites grow during development and are stable at maturity. The mechanisms that determine axon and dendrite size are not well understood. Here, we identify a cell surface protein, AMIGO1, that selectively promotes axon growth of horizontal cells, a retinal interneuron. Removal of AMIGO1 reduces the size of horizontal cell axons without affecting the size of their dendrites or the ability of both arbors to form connections. The changes in horizontal cell axons are matched by changes in synaptic partner dendrites to stabilize retinal function. This identifies territory matching as a novel homeostatic plasticity mechanism.
Topics: Animals; Axons; Dendrites; Mice; Retina; Retinal Bipolar Cells; Retinal Cone Photoreceptor Cells
PubMed: 35169021
DOI: 10.1523/JNEUROSCI.1164-21.2022 -
Advances in Experimental Medicine and... 2017This review discusses recent advances towards understanding the sigma-1 receptor (S1R) as an endogenous neuro-protective mechanism in the retina , a favorable... (Review)
Review
This review discusses recent advances towards understanding the sigma-1 receptor (S1R) as an endogenous neuro-protective mechanism in the retina , a favorable experimental model system. The exquisite architecture of the mammalian retina features layered and intricately wired neurons supported by non-neuronal cells. Ganglion neurons, photoreceptors , as well as the retinal pigment epithelium, are susceptible to degeneration that leads to major retinal diseases such as glaucoma , diabetic retinopathy , and age-related macular degeneration (AMD), and ultimately, blindness. The S1R protein is found essentially in every retinal cell type, with high abundance in the ganglion cell layer. Ultrastructural studies of photoreceptors, bipolar cells, and ganglion cells show a predominant localization of S1R in the nuclear envelope. A protective role of S1R for ganglion and photoreceptor cells is supported by in vitro and in vivo experiments. Most recently, studies suggest that S1R may also protect retinal neurons via its activities in Müller glia and microglia. The S1R functions in the retina may be attributed to a reduction of excitotoxicity, oxidative stress , ER stress response, or inflammation. S1R knockout mice are being used to delineate the S1R-specific effects. In summary, while significant progress has been made towards the objective of establishing a S1R-targeted paradigm for retinal neuro-protection , critical questions remain. In particular, context-dependent effects and potential side effects of interventions targeting S1R need to be studied in more diverse and more clinically relevant animal models.
Topics: Animals; Neuroprotective Agents; Photoreceptor Cells; Receptors, sigma; Retina; Retinal Diseases; Retinal Ganglion Cells; Retinal Neurons; Sigma-1 Receptor
PubMed: 28315278
DOI: 10.1007/978-3-319-50174-1_19 -
Neuroscience and Biobehavioral Reviews Dec 2016Proton magnetic resonance spectroscopy (H-MRS) has been widely applied in human studies. There is now a large literature describing findings of brain MRS studies with... (Review)
Review
Proton magnetic resonance spectroscopy (H-MRS) has been widely applied in human studies. There is now a large literature describing findings of brain MRS studies with mental disorder patients including schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorders. However, the findings are mixed and cannot be reconciled by any of the existing interpretations. Here we proposed the new theory of neuron-glia integrity to explain the findings of brain H-MRS stuies. It proposed the neurochemical correlates of neuron-astrocyte integrity and axon-myelin integrity on the basis of update of neurobiological knowledge about neuron-glia communication and of experimental MRS evidence for impairments in neuron-glia integrity from the authors and the other investigators. Following the neuron-glia integrity theories, this review collected evidence showing that glutamate/glutamine change is a good marker for impaired neuron-astrocyte integrity and that changes in N-acetylaspartate and lipid precursors reflect impaired myelination. Moreover, this new theory enables us to explain the differences between MRS findings in neuropsychiatric and neurodegenerative disorders.
Topics: Brain; Glutamic Acid; Glutamine; Humans; Magnetic Resonance Spectroscopy; Mental Disorders; Neuroglia; Neurons; Proton Magnetic Resonance Spectroscopy
PubMed: 27702600
DOI: 10.1016/j.neubiorev.2016.09.027 -
Progress in Retinal and Eye Research Sep 2019In this review, we summarize studies investigating the types and distribution of voltage- and calcium-gated ion channels in the different classes of retinal neurons:... (Review)
Review
In this review, we summarize studies investigating the types and distribution of voltage- and calcium-gated ion channels in the different classes of retinal neurons: rods, cones, horizontal cells, bipolar cells, amacrine cells, interplexiform cells, and ganglion cells. We discuss differences among cell subtypes within these major cell classes, as well as differences among species, and consider how different ion channels shape the responses of different neurons. For example, even though second-order bipolar and horizontal cells do not typically generate fast sodium-dependent action potentials, many of these cells nevertheless possess fast sodium currents that can enhance their kinetic response capabilities. Ca channel activity can also shape response kinetics as well as regulating synaptic release. The L-type Ca channel subtype, Ca1.4, expressed in photoreceptor cells exhibits specific properties matching the particular needs of these cells such as limited inactivation which allows sustained channel activity and maintained synaptic release in darkness. The particular properties of K and Cl channels in different retinal neurons shape resting membrane potentials, response kinetics and spiking behavior. A remaining challenge is to characterize the specific distributions of ion channels in the more than 100 individual cell types that have been identified in the retina and to describe how these particular ion channels sculpt neuronal responses to assist in the processing of visual information by the retina.
Topics: Amacrine Cells; Animals; Humans; Ion Channels; Retinal Cone Photoreceptor Cells; Retinal Ganglion Cells; Retinal Neurons; Retinal Rod Photoreceptor Cells; Synaptic Transmission
PubMed: 31078724
DOI: 10.1016/j.preteyeres.2019.05.001 -
International Journal of Developmental... May 2011Increased density and altered spatial distribution of subcortical white matter neurons (WMNs) represents one of the more well replicated cellular alterations found in... (Review)
Review
Increased density and altered spatial distribution of subcortical white matter neurons (WMNs) represents one of the more well replicated cellular alterations found in schizophrenia and related disease. In many of the affected cases, the underlying genetic risk architecture for these WMN abnormalities remains unknown. Increased density of neurons immunoreactive for Microtubule-Associated Protein 2 (MAP2) and Neuronal Nuclear Antigen (NeuN) have been reported by independent studies, though there are negative reports as well; additionally, group differences in some of the studies appear to be driven by a small subset of cases. Alterations in markers for inhibitory (GABAergic) neurons have also been described. For example, downregulation of neuropeptide Y (NPY) and nitric oxide synthase (NOS1) in inhibitory WMN positioned at the gray/white matter border, as well as altered spatial distribution, have been reported. While increased density of WMN has been suggested to reflect disturbance of neurodevelopmental processes, including neuronal migration, neurogenesis, and cell death, alternative hypotheses--such as an adaptive response to microglial activation in mature CNS, as has been described in multiple sclerosis--should also be considered. We argue that larger scale studies involving hundreds of postmortem specimens will be necessary in order to clearly establish the subset of subjects affected. Additionally, these larger cohorts could make it feasible to connect the cellular pathology to environmental and genetic factors implicated in schizophrenia, bipolar disorder, and autism. These could include the 22q11 deletion (Velocardiofacial/DiGeorge) syndrome, which in some cases is associated with neuronal ectopias in white matter.
Topics: Animals; Biomarkers; Bipolar Disorder; Brain; Endophenotypes; Humans; Nerve Fibers, Myelinated; Neurons; Schizophrenia
PubMed: 20691252
DOI: 10.1016/j.ijdevneu.2010.07.236 -
Psychiatria Polska Oct 2018Brain morphological changes in affective disorders occur mainly in the fronto-limbic cortex, hippocampus and amygdala - the structures regulating emotional and cognitive... (Review)
Review
Brain morphological changes in affective disorders occur mainly in the fronto-limbic cortex, hippocampus and amygdala - the structures regulating emotional and cognitive functioning, as well as development of somatic symptoms in the course of disorders. The largest number of reports of structural changes in the cerebral cortex include the dorsolateral prefrontal cortex, the orbitofrontal cortex and the anterior cingulate cortex. The results of neuroimaging and sectional studies reveal changes in the volume of structures involved in the creation of neuronal circuits that affect development of mood disorders. Microscopic studies show changes in cell count, density, and morphology in these areas. Some of those changes are observed only in certain layers of the cerebral cortex. A valuable addition to this data are histochemical studies of neuronal survival markers, proinflammatory cytokines, trophic factors, and markers specific for particular cellular structures. The role of monoaminergic, GABA-ergic and glutamatergic neurotransmission is confirmed by the studies on concentration of neurotransmitters, their receptors and transporters. Some of the results correlate quantitatively with the type and severity of symptoms, duration of the disorder, as well as pharmacotherapy and nonpharmacological treatment.
Topics: Bipolar Disorder; Brain; Humans; Mood Disorders; Neuroimaging; Neurons; gamma-Aminobutyric Acid
PubMed: 30584814
DOI: 10.12740/PP/89553