The Significance Of Calcium / Calmodulin-Dependent SKA II?

At the molecular level of explanation these processes are dependent on the interplay between glutamate receptors, Ca2+ channels, the increase of intracellular Ca2+ levels, Ca2+-dependent proteins like Akt, ERK, mTOR and neurotrophins such as brain derived neurotrophic factor (BDNF) (24, 25).

In a normal and healthy nervous system, many electrical signals are received and sent through neurons. The arrival of those signals at the end of the neuron triggers the release of many chemicals, in specific, neurotransmitters (Brooker, 2011). These chemicals travel into a gap between the presynaptic (end of one neuron) and the beginning of he postsynaptic (next neuron). This gap is named a synapse (Brooker, 2011). Neurotransmitters are then released into the synapse and then bind to the ibid (post -synaptic neuron). When this

NMDA Receptor is one of the crucial glutamate receptors present in the nerve cell. It gets activated when glutamate or Glycine binds to it. NMDA receptor is known for its role in synaptic plasticity and membrane function (learning and memory). Its activity is highly dependent on calcium influx. It is a tri heteromeric receptor with three different subunits NR1, NR2 and NR3. Each subunit has several other subunits, each of them having a unique function: NR1 has 8, NR2 has 4 (NR2A, NR2B, NR2C, NR2D), NR3 has 2 (NR3A, NR3B). Out of all the subunits, NR2A and NR2B have been extensively studied. NR2A, also known as GluN2A is believed to be involved in cell death pathways whereas NR2B, also known as GluN2B is believed to be involved in cell survival cascades (Bayer et al., 2006). Interestingly, GluN2B and GluN2A have differing roles, and both can affect either long-term potentiation (LTP) or long-term differentiation (LTD)

LTP can be divided into early and late phases. Early LTP sustains for 1-3 hours and requires covalent modification of pre-existing proteins and their trafficking at synapses, but does not need de novo protein synthesis. It can be induced by a weak, high frequency stimulus. Late LTP sustains for 8-10 hours in vitro and weeks in vivo, and requires new proteins synthesis and protein kinases activity, such as CaMKII, PKA and PKC. It can be induced by repeated strong high frequency stimulation, and plays a role in structural modification of synapses.

Overstimulation or prolonged activation of excitatory amino acid receptors is called excitotoxicity (64, 65). Overactivation of these excitatory receptors causes opening of post-synaptic ion channels which consequently increases intracellular Ca2+ and this affects Ca2+ regulatory mechanisms. Excitotoxicity seems to be a major contributor to many neurodegenerative disorders such as PD, AD and HD (65, 66). Although the pivotal role of excitotoxicity in neurodegenerative disorders has been proved, the exact mechanisms through which it promotes neurodegeneration still is unclear and more studies are needed (67). The N-methyl-D-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate (AMPA) subtypes are the main determinants,

Within the hippocampus, long-term potentiation (LTP) results due to the increased activity between a presynaptic and a postsynaptic neuron. The stimulation and subsequent depolarisation of a presynaptic CA3 pyramidal neuron results in the opening of voltage-gated calcium channels (VGCC). Thus, an influx in Ca2+ occurs, and glutamate vesicles are fused via synaptotagmin. The fusing of these vesicles allows the release of glutamate, a neurotransmitter which will bind to AMPA receptors and induce the influx of Na+ into the postsynaptic CA1 pyramidal neuron. This will result in the depolarisation of the postsynaptic neuron, which is one of the requirements for the opening and consequent induction of Ca2+ through the NMDA receptor. Through a cascade

The sodium-potassium pump plays an important role in depolarization and repolarization of the action potentials of the membrane. When the membrane is at resting potential, the sodium and potassium channels are closed. The stimulus starts the depolarization of the membrane to a threshold, after which sodium channels are opened. A large influx of sodium ions into the cell generates a positive membrane potential and causes rapid depolarization as a result of which an action potential is generated. As the membrane potential reaches +30 V, the sodium channels get inactivated, and the potassium channels are opened. The potassium ions move out of the cells beginning the repolarization of the membrane and restore it to its resting potential (Martini et al. pp. 408-409). These action potentials developed by the stimulus are carried by the axons of the sensory neurons to the CNS. The information carried by the action potentials is processed at every relay synapse, and is sent to the multiple nuclei and centers in spinal cord and brain (Martini et al. p. 510).

synaptic channels via NMDA-receptors, and which control gain through their voltage-dependent mode of operation. An impairment

The extracellular Na+ did not alter the membrane potential in the resting neuron because the Na+ channels were mostly closed.

This lecture started off with the description of two major synaptic influencers: the excitatory glutamate and the inhibitory GABA. Along with these

When neurons are exposed to excess levels of glutamate, they experience hyperactivation as they undergo physical alterations linked to changes in intracellular ion concentrations. Glutamate normally induces the opening of calcium ion channels on post-synaptic cells and, consequently, when excess glutamate remains in synaptic clefts it stimulates a higher influx of calcium into neurons. In rat cerebellar granule cells, calcium influx generated by neurotoxic glutamate levels was implicated in cell swelling and formation of aggregates within cell bodies.

Process called Synaptic plasticity plays a key role in memory and learning. Synaptic plasticity involves functional and structural alteration of synapses. CK2 has high catalytic activity phosphorylates serine and threonine residues in many proteins (Blankquest 2000) related to synaptic plasticity. CK2 is enriched in postsynaptic densities (Soto et al. 2004) crucial for synaptic

Does the activation of astrocytic CB1R facilitate excitatory currents in neighboring cells? Using immunostaining we will locate CB1R in astrocytes during critical periods and later. Next, using voltage sensitive dye imaging in IP3R2-KO mice in which astrocytic calcium surge is diminished, we will determine if critical period is affected. To confirm these results calcium imaging in astrocytes using Fluo-4 AM dye will be done [29]. Finally, we will use optogenetics to stimulate astrocytes at specific time points and using electrophysiology we will reveal if the excitation pattern of connected pyramidal cells are

The rhodopsin is a protein found within rod cells. As rhodopsin absorbs the light (photon), it causes metarhodopsin II to be produced. This ends up activating a protein called transducin by switching GDP with GTP on this protein. At this point, transducin is activated, and it ends up activating phosphodiesterase, which causes cyclic GMP to decrease, which in turn causes Na+ channels to close. As a result of this, hyperpolarization occurs, and nerve impulse is sent to the brain.

Restructure of synapse types and alternations of dynamics of neurotransmitters and neuromodulators have been implicated in a number of human neurological and psychiatric diseases, including autism, Alzheimer’s disease, Parkinson’s disease, schizophrenia, and addiction1,2. However, little is known about how molecular compositions define different types and functions of synapses and how different synapses organize in micro- and macroscale to give rise to complex brain functions and disorders, due to lack of appropriate tools to characterize synaptic biomolecules in situ in large scale. Here, I propose a novel research program to develop transformative tools for large-scale mapping of synaptic biomolecules, functional imaging of neurotransmission and neuronal signaling. Specifically, it will evolve along three main themes: 1. Expansion pathology for highly multiplexed, in situ and nanoscale biomolecular imaging. 2. Optogenetic neurotransmitter indicator; 3. in situ imaging tools for endogenous protein-protein interaction; This program will expand on the themes of my previous work on engineering optogenetic indicators for neuronal activities, such as calcium ions3,4 and voltage5,6 indicators, as well as my current work on devising a clinically optimized form of expansion microscopy7,8, which contribute new capabilities to the broader communities of neuroscience, cell biology, pathology and medicine.