# The Impact of Optogenetics on Regenerative Medicine
## 2 Molecular Pathways in Optogenetics
The optogenetics strategies can be used to selectively activate a specific group of neurons through the activation of membrane channels or pumps, via second messengers. Recently, this technique has been used to better understand the functional properties of nociceptive cutaneous activation of the Nav 1.8 tetrodotoxin-resistant voltage-gated channel. The sensitivity to blue light (470 nm) of the ChR2 is decisive for the activation of Nav 1.8 channels and the stimulation of several nociceptors. The stimulation by specific lights can lead to the depolarization of the neuronal membrane, inducing the opening of Nav 1.8 [15]. The neurons activated by Nav 1.8 are typically sensitive to thermal and mechanical stimuli. Thus, with optogenetics, light provides a non-invasive stimulation that activates specific biological structures that are difficult to stimulate with standard techniques [16; 17]. Considering its peculiarities, Optogenetics may be considered as a reliable tool for the study of the dopaminergic system. Recently, [PERSON] et al. [18] conducted a study on the effects of dopamine obtained by the stimulation with optogenetic techniques. As known, dopamine is a neurotransmitter with several functions; its control depends on the mesolimbic system in which dopamine regulates the synaptic weights. The study performed by [PERSON] et al. [18] consisted of in vivo experiments aimed to evaluate the efficacy of optogenetic techniques, in comparison with the electronic stimulation. In this context, the optogenetic-induced intracranial self-stimulation is a helpful tool to study the effects of dopamine release in the healthy and pathological human brain. Under light stimulation, the ChR2 located in the VTA (ventral tegmental area) cells can induce dopaminergic self-stimulation, capable of evading sensory limitations. For example, a sense of appetite or satiety can be evoked, and thus investigated in depth [19]. Applications for Cellular Communication  
During the embryonic development, a dynamic coding can play an important role in cell-to-cell communication. The duration of the stimulus is an important factor for the development of proper cell responses: in this context, an optogenetics approach may offer an interesting opportunity to modulate signaling paths with high precision and in real time. In several studies on somitogenesis, the somites have been studied during their generation by the presomitic mesenchymal mesoderm (PSM). These somites will develop bones, skeletal muscles, and subcutaneous tissues. The optogenetics approach has been used to investigate the processes of the spatial evolution and the temporal genetic coding, analyzing the frequencies of such signals that stimulate and inhibit embryonic development [20; 21]. Several optogenetic-based techniques have been developed in recent years: some of them are currently applicable to TERM. Functional optogenetic tools are safely usable in human cells, by modulating specific parameters, such as wavelength, duration, or energy emitted by laser devices [22]. Ultraviolet (UV) receptor systems are also used in optogenetic applications: they are easily controllable, and they work with both normal light or lasers [23]. A novel technique is the light-oxygen-voltage (LOV): LOV tools are used to control such signaling characterized by a rapid kinetic, such as ion channels and protein kinases [24]. Cryptochrome systems are characterized by Cryptochrome 2 photosensors (CRY2) and cryptochrome-interacting basic-helix-loop-helix (CIB1), sensitive to blue light. Such systems are also suitable for the detection of signal cascades showing a rapid kinetic [25]. In 2017, [PERSON] et al. [26] reported two-way photocontrol systems without cofactors, using a specific protein, the Dpropna145N, able to ensure more flexible manipulation of the target proteins, revealing all the possible states of activation. Recently, cobalamin-based systems (CBD) have been involved in optogenetic tools, in the green spectrum with a specific activation with vitamin B12 and AdoB12.