**6.1 Mosquito sialome leads to feeding success**

To feed on a vertebrate host, the arthropods are required to overcome a series of obstacles [86]. The saliva produced by the hematophagous insects contains bioactive molecules that counteract host defense [91]. Mosquitoes are reported to feed on arterioles and venules rather than capillaries, and they often probe multiple times at different sites to find a suitable site for feeding [86]. Initiation of feeding induces hemostatic cascade within the host including the platelet aggregation followed by collagen interaction with ADP which supports the blood coagulation pathway [87, 92]. The presence of secretory apyrase enzyme in the salivary gland of blood-feeding arthropods inhibits platelet aggregation by hydrolyzing ATP and ADP into AMP and inorganic phosphate [93]. Vasoconstriction is a common phenomenon following laceration of blood vessels due to insect bite to minimize blood flow and hence loss of blood [87]. The hematophagous insects, including *Aedes aegypti* mosquito saliva, contain sialokinins which act as a vasodilatory molecule by stimulating nitric oxide (NO) production by the endothelial cells via cGMP induction [87, 94, 95]. Except apyrase and sialokinin, salivary specific D7 family proteins have been implicated to function as a scavenger molecule of serotonin, histamine, and norepinephrine and antagonize their vasoconstrictor, plateletaggregating, and pain-inducing properties [94, 96]. Salivary peroxidases are well known for their potent function as a vasodilator, as it might act as a hydrogen peroxide-dependent destructor of serotonin and noradrenaline [97]. Furthermore, the secretory anophelin protein is reported to inhibit thrombin activity and collagen sequestration and hence delay platelet aggregation [98]. An additional challenge arises from the immune components of the blood meal itself which have been generated during previous exposure of mosquito bites [86]. Thus, successful blood feeding is dependent on the evolution of salivary composition possessing anti-immune molecules to suppress the action of host immune factors. Antitumor necrosis factor in female salivary glands is one of the crucial molecule that may play anti-immune function in hematophagous insects [86].

**85**

**Figure 5.**

*the navigation process by induction of salivation.*

*Neuro-Olfactory Regulation and Salivary Actions: A Coordinated Event for Successful…*

The experimental evidence about the classical conditioning of salivation in dogs was demonstrated by Pavlov in the early nineteenth century [99, 100]. By definition, classical conditioning refers to the learning procedure where a conditioned stimulus (CS), for example, the sound of a bell, is paired with an unconditioned stimulus (US), such as food which eventually triggers salivation [100], although secretion of saliva is obligatory to facilitate feeding for majority of animals from invertebrates to vertebrates. However, the knowledge of classical conditioning of salivation is restricted to mammals and invertebrate cockroaches [99]. The salivary gland and the saliva make the bridge that joins the mosquito vectors, parasite, and the host together by facilitating blood meal uptake and parasite transmission [86]. But, the cellular and molecular mechanisms underlying the classical conditioning of salivation in mosquitoes remain unknown. Considering the finicky host-seeking behavior of mosquitoes and their preference towards a certain host [47], it can be hypothesized that mosquitoes can learn during the repeated exposure of conditioned stimulus such as host odor and unconditioned stimulus, which is a reward of blood meal [47]. Reward may be appetitive when mosquitoes get benefited from the blood meal or aversive if mosquitoes experience any kind of host defensive behavior [47]. Thus, it can be speculated that mosquitoes should exhibit classical conditioning of salivation, i.e., increase saliva secretion which is tightly regulated by the

Our knowledge about control of insects' salivary secretion is limited to cockroaches, locusts, and blowflies, where neuronal innervation of the salivary gland or neuro-hormonal regulation was reported to play a significant role in salivation [101, 102]. Insects' salivary glands are innervated with nerves that are originated from different sources of the central nervous system [102]. Stomatogastric nervous system projects its nerves in the salivary gland of *Manduca sexta* [103]. The salivary gland of cockroaches (*Periplaneta americana*) is innervated with nerves that are projected from both the stomatogastric system and the subesophageal ganglion [102, 104, 105]. An exception to that is that the blowfly salivary glands are not innervated, but the salivary secretion is regulated by the secretion of the biogenic amine serotonin [102, 106]. Gustatory stimulation leads to the release of

*Graphical illustration of conditioning of salivation in mosquitoes. Mosquitoes navigate towards vertebrate host through olfaction when they sense the odor plume emanating from the host (both appetitive and defensive). Olfaction also induces the salivary secretion (conditioning of salivation) with the aim to facilitate blood meal uptake. But the host's defensive behavior interrupts successful encountering of the mosquito with the host (redcolored human), which mosquitoes can memorize, and during consecutive exposure they probably restrict the salivation process to avoid the respective host, whereas mosquitoes get a reward from the appetitive host through successful blood-feeding without any interference. This positive memory along with olfaction further empowers* 

*DOI: http://dx.doi.org/10.5772/intechopen.90768*

**6.2 Neurological control over salivation**

neuro-olfactory system (**Figure 5**).

*Neuro-Olfactory Regulation and Salivary Actions: A Coordinated Event for Successful… DOI: http://dx.doi.org/10.5772/intechopen.90768*
