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Of particular interest is the Ca 2+ conductance based on T type Ca 2+ channels that gives rise to I T (Jahnsen and Llinas, 1984; Sherman, 2001; Sherman and Guillery, 2006). I T is an inward current that produces a transient depolarization of the cell. While T channels are common to neurons everywhere, providing for depolarization, what sets the thalamic relay cell somewhat apart is that it exhibits a sufficiently dense distribution of T channels in its soma and dendrites that initiation of I T generally leads to an all-or- none Ca 2+ spike that propagates throughout the soma and dendritic arbor. Every relay cell in every thalamic nucleus of every species studied so far shows this behavior, and this is seen only rarely in other neuronal types in the central nervous system .

Figure 2: Schematic representation of actions of voltage dependent T (Ca ) and K conductances underlying low threshold Ca spike; redrawn from (Sherman and Guillery, 2006). The sequence of events is shown clockwise in A-D, with the membrane voltage changes shown in E. A: At a relatively hyperpolarized resting membrane potential (roughly -70 mV), the activation gate of the T channel is closed, but the inactivation gate is open, and so the T channel is deactivated and de-inactivated. The K channel is also deactivated. B: With sufficient depolarization to reach its threshold, the activation gate of the T channel opens, allowing Ca to flow into the cell. This depolarizes the cell, providing the upswing of the low threshold spike. C: The inactivation gate of the T channel closes after roughly 100 msec ("roughly", because closing of the channel is a complex function of time and voltage), inactivating the T channel, and the K channel also opens. These combined actions repolarize the cell. D: Even though the initial resting potential is reached, the T channel remains inactivated, because it takes roughly 100 msec of hyperpolarization to de-inactivate it; it also takes a bit of time for the various K channels to close. E: Membrane voltage changes showing low threshold Ca spike.

The figure shows the voltage and time dependency for the T channels (Jahnsen and Llinas, 1984; Sherman, 2001; Sherman and Guillery, 2006). These channels can be both activated and inactivated by voltage, and thus have two voltage gates. At rest (e.g., roughly -70 mV or so), the inactivation gate is open but the activation gate is closed, and so the channel is both de-inactivated and deactivated (panel A). If the cell is then depolarized to threshold for the activation gate (to roughly -65 mV), the activation gate pops open, leading to the inward I T , which, in turn, activates the upswing of the all-or-none Ca 2+ spike; in this state, the T channel is activated and de-inactivated (panel B). After roughly 100 msec of depolarization, the T channel inactivates (panel C), and this, along with activation of a slower series of K + conductances, leads to repolarization of the neuron. Here, the T channel remains inactivated (panel D) for another 100 msec or so, after which time the original state of panel A is returned. The two gates of the T channel have opposite voltage dependencies, but while the activation gate responds quickly to voltage change, the inactivation gate is slower, requiring roughly 100 msec of polarization change to open or close. Actually, inactivation and de-inactivation are complex functions of voltage and time so that the more the cell is depolarized, the faster I T inactivates, and the more the cell is hyperpolarized, the faster I T de-inactivates. This requirement of roughly 100 msec of hyperpolarization to de-inactivate the channel provides a refractory period that limits low threshold Ca 2+ spiking to \leq 10 Hz.

Oral ingestion produces good non specific immune response and can be the most cost effective method with economically viable. It is mostly suited for extensive aquaculture system. Immunostimulants powders are mixed with feed using a fish oil coating. Now a day, bioencapsulation method is also followed to immunize the fish larvae during their early larval stages with live fed organisms.

Timing of administration

It is necessary to apply immunostimulants at the right time. Anderson [ 4 ] proposed that the application of immunostimulants should be implemented before the outbreak of disease to reduce diseaserelated losses. Effective dosage and exposure time will be further more complicated based on different culture systems with feeding regime [ Outlet 100% Authentic BASKET HEART PATENT Trainers white Clearance Cheap Finishline Cheap Online Under Sale Online BIo0EhRN
]. In Atlantic salmon injection with high dose of glucans @ 100 mg/ kg led to absence of protection for 1 week, but maximum benefits only occurs after 3-4 weeks. Also, at low dose of injection @ 2-10 mg/kg, give protection only 1 week [ 32 ]. Similarly, it has been noticed that increase in the number of NBT positive cells in African Catfish fed with glucan or oligosaccharide over 30 days, but not over 45 days [ 57 ].

Mode of action

The mode of action of immunostimulants is to activate the immune systems of organisms, to enhance the immunity level against invading pathogens. The approach is very diverse in nature or may be poorly understood and also depends on the type of immunostimulants, dose, route of administration, time and length of exposure.

Following are some of the mechanism of actions:

• Stimulators of T-lymphocytes- Levamisole, Freund’s Complete Adjuvant (FCA), Glucans, Muramyl dipeptide , FK-565 (Lactoyl tetrapeptide from Streptomyces olivaceogriseus ).

• Stimulates of B-cells- Bacterial endotoxions, Lipopolysaccharides.

• Macrophage activator- Glucans, Chitin and Chitosan

• Inflammatory agents including chemotoxins

• Cell membrane modifiers- Detergents and Sodium dodecyl sulphate, Quaternary ammonium compounds (QAC), Saponins

• Nutritional factors- Vitamin C and E, n-3 fatty acids

• Cytokines- Leukotriene, Interferon

• Heavy metals- Cadmium

• Animal and fish extracts- Mitogens

In general immunostimulants enhance the phagocytosis and bacterial killing ability of macrophage, complements, lymphocytes and nonspecific cytotoxic cells, resulting in resistance and protection to various diseases and invading microorganisms.

Detection of immunostimulation

An increase in any characteristics such as phagocytosis, production of superoxide anions etc in treated fish and shellfish over controls is evidence of immunostimulation. Following are some of the methods of detection of immunostimulation.

1. Haematocrit and leucocyte count: Leucocytes mediate nonspecific immunity. So raised leucocytes count with an essentially unchanged haematocrit is an indication of immunostimulation.

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