Abstract
Bipolar cells serve as the bridge cell between the photoreceptor cell and the ganglion cell that located in the INL and span from the OPL down towards the IPL of the retina. Like the photoreceptor cell it also must transduce a chemical signal in order to signal ganglion cells or amacrine cells. The transduction pathway in the bipolar cell is different from the photoreceptor transduction pathway in that there are two distinct bipolar cells that do not use photons as the trigger but instead the neurotransmitter glutamate that is activated by hyperpolarization of the photoreceptors. ON-bipolar cells are depolarized by a central stimuli to the receptive field that is position in the center while OFF-bipolar cells are hyperpolarized by
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light stimulation of the peripheral receptive field locate around the center. Bipolar cells are modulated by nyctalopin complex as well as calcium ions, thought the extent of the nyctalopin complex as well as a second messenger signal between GO and TRPM1 channel is being studied further. Introduction The ocular system consists of the eye and its central visual system that integrate into the nervous system. Light from the outside passes through the central visual system consisting of the cornea, the lens, and aqueous humor that then reaches the retina. The retina then generates signals passed by the optic nerve to the brain and interpreted as vision. The ocular system allows the body to see the outside world. The mammalian retina is a highly operational extension of the nervous system that responds to light stimulus (1). This highly evolved organ is responsible for not only capturing light stimulus but also the interpretation of that stimulus. The interpretation of the light stimulus is what gives vision and forms the light image that is perceived through the ocular system. The retina contains two types of photoreceptors, rods and cones. The rods are more numerous and are more sensitive than the cones, however, they are not sensitive to color. The cones provide the eye's color sensitivity and they are much more concentrated in the central region of the retina known as the macula (2). In the center of this concaved area the structure that forms the central vision or fovea centralis is found, this is a rod-free area with very thin, densely packed cones. The retina is able to transform the photon energy into signals through polarization of unique cells (3).
Within the retina lay different cells capable of handling and directing different pathways. From the photoreceptors, to horizontal cells, bipolar cells, amacrine cells, and the ganglion cells. Of these cells it is the bipolar cell which conducts visual signals to the brain using parallel ON-Center and Off-Center pathways (4). The pathways these signals travel from the bipolar cells are considered ON when depolarized and when OFF are hyperpolarized. In the mammalian retina metabotropic glutamate receptors (mGluRs) are associated with the ON pathway and ionotropic glutamate receptors (iGluRs) are associated with the OFF pathway …show more content…
(5). In the following text a representation will be outlined that covers the bipolar cells. The topics will include a brief explanation of the differences in bipolar cells but keeping in note that more bipolar variants exist than the two broad categorized ON/OFF-bipolar cells. The ON-bipolar cell is usually the most studied because of its intrinsic pathway which aids in relay signaling and for that matter will be covered greater in detail. The discussion will also cover TRPM1 channels and the importance they hold when associated with mGluRs. Also the importance of nyctalopin complex will reviewed as well as what affect calcium ions play in the transduction pathway of bipolar cells. The purpose of this paper is to establish a synopsis of what a bipolar cells’ function and physiology is and why they are important as well a brief comparison to the phototransduction pathway that is the preliminary cascade that must occur in order for the proper neurotransmitter to be released that activated the bipolar cells’ pathway. Discussion Difference in Bipolar cells Distinguishing from the two main types of bipolar cells, ON and OFF, can be done by their function and unique cell morphology. While OFF retinal bipolar cells express α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors otherwise known as AMPA receptors in their dendrites, and at times kainite receptors. The ON retinal bipolar cells use metabotropic glutamate receptors group III, subunit six or mGluR6 to close a postsynaptic channel, transient receptor potential-melastatin 1 (TRPM1) through a G-protein coupled mechanism (6). Morphologically, the OFF RBC dendrites have their synaptic region contact the base of the photoreceptors near the base of the presynaptic terminal and the ON RBC dendrites are located at the center of the triad complex with the horizontal cells’ dendritic process on either side. The axon terminals for both ON and OFF RBC’s within the inner retina terminate at a different region in the inner plexiform layer (IPL) (6). Figure 1 illustrates the position of the different bipolar cells the physiology of the retinal layers. The ON-Bipolar Cell When ON RBC’s are subject to light the conductance of these cells increases.
The implication for this occurrence is that glutamate must block a certain cation-permeable channel keeping the cell continuously depolarized (7). The mGluR6 couples to heterotrimeric G protein complex, known as GO. For phototransduction to occur the GOα ¬ complex must be able close the non-selective melastatin-related transient receptor-1 (TRPM1) cation-channel at the moment when activation of the ON bipolar cell occurs (8). The mechanism of exactly how this complex was able to close the cation-channel was unknown until recently. The dominant α subunit of the G¬O is Gαo and Gαo2 has been noted to help during the ON polar light response (9). Furthermore, Gβϒ in the latest studies in many signaling processes has shown to act differently with different effectors giving array to a multitude of assembly and movement of receptor based signaling complexes (9). Because of Gβϒ there has been signaling mechanisms based on G-proteins range that has increased its
versatility. TRPM1 TRPM is expressed primarily in the bipolar cells in the visual pathway but can be found in a number of other sensory organs that have cation-channels that lack voltage (10). In recent studies of the ON bipolar cell a non-selection ion channel has been observed downstream in the cascade from the mGluR6. This ion channel is described at a TRPM1-L channel that that is regulated by the Gαo subunit (8). TRP channels are in various animal groups and with at least 28 subtypes that have been discovered(11). These subtypes are divided into two groups, while the first group contains the melastatin or TRPM1-L channel located in the ON bipolar cell. Similar to the G-protein complex TRP channels are found throughout different sensory systems such as auditory, gustatory perception, thermoception, and osmoregulation and can be found in some human disease (11). These channels in the retina or located on the photoreceptors, amacrine cells, and ON-bipolar cell types. Here the ON-bipolar cells are antigenic to the TRPM1 channels though marking has placed them within the cell bodies and axons, see Figure 1.A. (8). Also, TRPM1-L channel has been associated or known to couple to mGluR6 (8). Because the cells that express only mGluR6 and Gαo or Gαo and TRPM1 are normally unresponsive to glutamate researchers firmly believe that the TRPM1 channels are located downstream from the mGluR6 receptors (8). This indicates that both the TRPM1 and the mGluR6 channels are absolute to the ON-biploar cell response when light evokes a response. Nyctalopin Complexes In a recent study produced by Yan Cao reports that the nyctlopin complex modulates the TRPM1 channels and is a key component of the receptor-channel affecting the structure (12). This synaptic protein nyctlopin might be responsible for the fast transmission rate of the signaling that occurs in bipolar cells from the mGluR6 to the TRPM1 (12). Yan Cao also reported that without this complex the proper configuration would not be established diminishing the possibility of the required threshold being reached to produce a light response (12). Calcium Ions (Ca2+) The Ca2+ ions play a modulator role in the metabotropic glutamate receptor by allowing the ions to enter through TRPM1 channels (7). When the TRPM1 channel is flooded with the Ca2+ ions it activates calcium-dependent enzyme CaMKII that modulates the flow (13). In Nawys’ study it was observed that the Ca2+ ions triggered a negative-feedback pathway and when glutamate fail the ions were allowed to enter causing repolarization and restoring the membrane potential to the state as it was before a light response was triggered (7). The association between mGluR6 and Ca2+ provides a coping mechanism in which the photoreceptors can quickly adjust to changes in low light (7). OFF-Bipolar Cells The different intrinsic properties of the different bipolar cells allow the signals from a cone to be directed into separate pathways. It is the distinct morphological physiology of these cells and uniqueness of the GluRs found the dendrites that allow this. The glutamate receptors that are expressed in an OFF-bipolar cell are ionotropic consisting of NMDA, AMPA, and Kainate. Though NMDA is not a part of the light response, AMPA and kainite receptors are but perform differently when glutamate evokes a response (14). One difference is that each receptor sensitizes at a different rates after desensitization occurs while kianate receptors are less selective than AMPA when signaling (14). Phototransduction Bleaching occurs when retinal chromophore isomerizes from an 11-cis configuration to an all-trans molecule. This action then produces a cascade starting with the activation of metarhodopsin II that activates G-protein transducin, cGMP-phosphodiesterase is formed which occurs when cGMP become hydrolyzed resulting in the cGMP-gated cation channel closing (15). This then produces hyperpolarization of the photoreceptor causing the release of the neurotransmitter glutamate (15). Of these photoreceptors the rods are 100 fold more sensitive than cones reacting to even one indivual photon (15). Also the photoreceptors have distinct capabilities beside light/dark functions, within these specified functions lay specific attributes. For instance rods experience longer refractory periods following bright light exposure while cones recover within minutes and even being able to adjust to different brightness levels or intensity to keep visual process active (15). For comparison Figure 2 illustrates the difference between rod and cone sensitivity. Another interesting thing that happens only in phototransduction is the recycling of chromophore. This occurs in the retinal pigmented epithelium where the all-trans chromophore is converted back into 11-cis chromophore by a process involving reactions catalyzed by enzymes. These enzymes can be found in Mueller cells where the process takes place as cones specifically oxideize the 11-cis chromophore (15). See Fig 3. For the details of this unique process. Conclusion In conclusion there are different types of bipolar cells, the ON/OFF-bipolar cells span into several layers of the retina. It was not introduced in much detail but the physiology of retinas differ amongst species and the mammalian and vertebrae retinas are the focus of this text. What has been studied and reviewed is that there are modulators in the pathway of bipolar cell transduction. That mGluR6 and TRPM1 are the primary corresponding structures responsible for the signaling of the bipolar cell onto ganglion cells and amacrine cells. We also know that calcium affects the modulation or how the cells repolarize by reducing the flow of certain ion channels. Furthermore need to study the extent of which the nyctlopin complex affects or regulates the physical structure of the cells and what other complexes might exist that aid in the signaling cascade. The machinery that drives both rod and cone bipolar cells is similar and very little is known about the differences. There are the ionotropic and metabotropic differences that have been studied and compared but that seems to be the surface of exactly how each cascade differs. More studies need to be conducted to evaluate the latency between the two different cells and well as how much the different types of bipolar cells differ physiologically.
Stone, J. (1972). Morphology and physiology of the geniculocortical synapse in the cat: The question of parallel input to the striate cortex. Investigative Ophthalmology & Visual Science, 11, 338-46.
G-protein-linked receptors are protein receptors, located in the plasma membrane of a cell, that work with G-proteins to activate a cell-signaling pathway. These receptors are structured similarly in most organisms, with seven α helices and specific loops for binding sites for signal molecules and G-proteins. When a signal molecule from the extracellular fluid attaches to the signal-binding site it activates the G-protein-linked receptor by changing its shape. When this happens, the G-protein, loosely attached to the cytoplasmic side of the cellular membrane, attaches to its binding side on the receptor protein. The inactive G-protein becomes activated when GDP is displaced by GTP, a molecule similar to ATP. When the signal molecule is released, the G-protein diffuses along the cell membrane and attaches to an inactive enzyme. This newly activated enzyme triggers the cellular response. When the protein detaches itself from the enzyme, it releases a phosphate group turning GTP back into GDP, making the G-protein inactive once again.
I have chosen to do a paper on Bipolar Disorder. Bipolar is a disorder in when a person’s mood inappropriately alternates between feelings of mania and depression. A bipolar mania is a mental illness classified by psychiatry as a mood disorder. Also individuals with bipolar disorder experience episodes of an elevated or agitated mood known as mania or hypomania, depending on the severity alternating with episodes of depression.
Eric Beck meets criteria for Bipolar 1 disorder. He shows some signs of General Anxiety Disorder as well. Anxiety disorders are the most coming co-occurring disorder with Bipolar 1. To be diagnosed with Bipolar 1 disorder you must meet criteria for Major Depressive Episode and Manic Episode. Eric meets criteria for part A of Major Depressive Episode due to his extensive history of depression. He stated that “I suffer even when doing things, I should enjoy.” He often had feelings of guilt or worthlessness. Along with this Eric struggled from a lack of concentration. He also had recurrent thoughts of death and has tried to commit suicide.
Action potentials in neurons are facilitated by neurotransmitters released from the terminal button of the presynaptic neuron into the synaptic gap where the neurotransmitter binds with receptor sites on the postsynaptic neuron. Dopamine (DA) is released into the synaptic gap exciting the neighboring neuron, and is then reabsorbed into the neuron of origin through dopamine transporter...
glutamate receptors using antibodies, that tag on to the receptor itself. The proteins that make up the
These electrical signals arise from ion fluxes produced by nerve cell membranes that are selectively permeable to different ions. Neurons and glia (cells that support neurons) are specialized cells for electrical signaling over long distances. Understanding neuronal structure is important for understanding neuronal function. The number of synaptic inputs received by each nerve cell in our (human) nervous system varies from 1-100,000! This wide range reflects the fundamental purpose of nerve cells, to integrate information from other neurons.
Bipolar II disorder is a treatable mental illness that is often confused with Bipolar I disorder. The two are similar but still have many differences such as with Bipolar II it consists of two main symptoms, depression and hypnomania. The major difference between bipolar I and bipolar II is that with bipolar II the patient never reaches a full state of mania, rater they experience hypnomania which is a less elevated form of mania; where with the depression aspect of the disorder it can last much longer in bipolar II than in bipolar I. There are around 6 million people currently in the United States who suffer from some form of bipolar disorder yet most people don’t really have an accurate perception of what this condition is or how life is for those living with it.
Bipolar Disorder can be classified by the occurrence of manic episodes followed by hypomanic or major depressive episodes. A manic episode is a distinct period of abnormally and persistently elevated, extensive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day. During the specific period of mood disturbance and increased energy or activity, many symptoms are present. Some examples of these symptoms can include: -Inflated self-esteem or grandiosity, decreased need for sleep, and are more talkative than usual (“Bipolar and Related Disorders, “n.d.). There is a 10- 15% risk of completed suicide associated with Bipolar Disorder (“Bipolar Depression”, 2)
Q1.The cell cycle is the series of events which occur in a cell leading to its division and replication.
... over normal proliferating cells (Figure 1) It is important to target events taking place at the same time in the cell cycle in order to boost effectiveness of the arrest and the results. In addition, it is important to characterize tumors precisely in order to clarify where the deficiencies on the cell cycle control are accrued and which of the phases have to be targeted for successful therapy. Furthermore, in the future, identification of new tumor specific isoenzymes will be necessary to characterize the cell cycle accurately and comprehend the differences between normal cells and cancer cells for the design of novel anticancer therapies (Diaz-Moralli, et al. 2013).
The cell cycle is the process by which cells progress and divide. In normal cells, the cell cycle is controlled by a complex series of signaling pathways by which a cell grows, replicates it’s DNA and divides, these are called proto-oncogenes. A proto-oncogene is a normal gene that could become an oncogene due to mutations. This process has mechanisms to ensure that errors are corrected, if they are not, the cells commit suicide (apoptosis). This process is tightly regulated by the genes within a cell’s nucleus. In cancer, as a result of genetic mutations, this process malfunctions, resulting in uncontrolled cell proliferation. Mutations in proto-oncogene or in a tumour suppressor gene allow a cancerous cell to grow and divide without the normal control imposed by the cell cycle. A change in the DNA sequence of the proto-oncogene gives rise to an oncogene, which
Bipolar disorder is also known as manic-depression disorder, may cause unusual changes in mood and behavior such as grandiosity, decreased energy, distractibility, diminished interest, insomnia, pressured speech, suicidal thoughts, and decrease in the ability to carry out day to day tasks (Diagnostic and Statistical Manual of Mental Disorders; 5th Ed.; DSM-5; American Psychiatric Association, 2013). According to Jann (2014) the symptoms of bipolar disorders are severe alternating between normal ups and downs leading in damaged relationships, poor job and school performance, and even suicide among the most severe. There are four types of bipolar disorder which include bipolar I disorder, bipolar II disorder, bipolar disorder not otherwise specified, and cyclothymic disorder Jann (2014).
The retina contains rods and cones which detect the intensity and frequency of incoming light and, in turn, send nerve impulses to the brain.
Bipolar disorder is a lifelong condition that can affect how you feel and how you act. It is a mood disorder caused by chemical imbalances in the brain that can result in extreme mood swings, from manic highs to depressive lows. Also known as manic-depressive disorders, bipolar disorder is categorized and determined as “a psychological state in which a person experiences a mood disorder causing radical alterations in their moods”. Elevated levels of either manic or depression are very common with a person affected by a bipolar disorder.