**4.1 Mechanisms of memory formation**

According to human physiology, memory is a phenomenon that takes place in the following structures: the hippocampus and the cortex (specifically the neocortex) [17]. Moreover, memory cannot be described as an isolated phenomenon since the cortex and limbic system takes place in memory consolidation. The amygdala plays a fundamental role in emotional response linked with memory being fear, one of the principal factors for plasticity and neurochemical activities in that anatomic region [18, 19]. It is important to state that the relationship between the amygdala and hippocampus balances the encoding processes of memory [20]. Also, it has been determined that the cingulate cortex is involved in action-outcome learning, and it also is an important place of brain connectivity [21].

It is important to mention that memory has also a neurophylogenetic component. Chittka described that many animals such as wasps, bees, and cockroaches have the ability of spatial learning for surviving [22]. Decapod crustaceans have the same ability as well, it has been published that crabs can adapt and be conditioned to solve mazes having an improvement in comparison with those who did not have time to explore the trial [23]. Krichbaum reported that dogs have the capability of episodic memory for accomplishing tasks, even though seven out of ten dogs tested positive in conduct


#### **Figure 2.**

*It is demonstrated the memory function: short-term, working memory and long-term with its main characteristics and examples of each subtype.*

experiments, more research should be done to clarify this proposal [24]. According to scientific literature, monkeys can retrieve information from short to medium periods of time, use working memory, and have a limited self-perception when answering cognitive tests [25]. Humans are at top of this evolutionary scale due to their complex brain structure and functional morphology, that no other species own.

It might sound coherent to the fact that the cortex is involved in decoding the diverse stimuli that pass through the senses (*i.e.,* sight, touch, smell, taste, hearing, cognitive estimation, and reasoning). Memory is determined by several factors such as chemicals, hormones, neurotrophic factors, neurotransmitters, external stimuli, and sleep.

Regarding sleep, Klinzing determined that Long-Term Memory is formed during slow-wave sleep in the hippocampus of rodents, so as in humans [26]. Speaking about hormones, it has been described by Acosta that the circadian rhythm plays an important role in starting and stopping the gene and cellular structures that are regulated by an extensive number of hormones (*i.e.,* Cortisol, Digestive Hormones) [27]. Also, the relationship between hormone regulation and the gut-brain axis (GBA) has a fundamental role with the hypothalamus in maintaining a healthy metabolism and a correct function of glutamatergic, cholinergic, calcium-calmodulin, mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases (ERK's), phosphoinositide 3-kinase (PI3K), ghrelin, leptin, insulin, and glucagon signaling [28].

Also, one of the most recent studies has determined that smoking cannabis containing the active molecule of tetrahydrocannabinol (THC) disrupts short memory, but unclear evidence of neurogenesis in the hippocampus also has been reported [29]. Alcohol abuse in big quantities can prevent the brain from forming new memories, and after the withdrawal, incapacity to remember correctly what happened when drunk. Also, it has other metabolic consequences [30].

Moreover, the hippocampus builds coherent long-lasting memories, merging exploratory visual exploration and memory formation [31]. Adding that also the other senses can take place in this process. The reality is that the theory of engrams "basic biological unit of memory" has been merged with neuroplasticity to understand the physiological mechanism of forming memories [32]. As it has been stated, reducing complex processes: in this case, a "memory to an engram" also can bring detrimental consequences for scientific research.
