The Psycho - Neuro - Humoral Connection

The thought (perception) memory, smell, sight, and taste of food stimulates the production of saliva.  The cephalic phase of digestion is governed by the Autonomic Nervous System (ANS) and regulated by the hypothalamic region of the brain. The ANS involuntarily regulates digestion, as well as many other bodily functions, internal organs and glands.

The hypothalamus receives ANS regulatory input from the limbic system and integrates that information into autonomic functions across the three subdivisions of the ANS that emerges from the craniosacral and thoracolumbar areas of spinal cord.

The Autonomic Nervous System (ANS)

• Parasympathetic (PSNS) - Craniosacral Nerves

• Sympathetic (SNS) - Thoracolumbar Nerves

• Enteric (ENS) (addressed in next article)

The Parasympathetic Nervous System (PSNS) stimulates salivation and digestion aka rest and digest; while the Sympathetic Nervous System (SNS) is responsible for stimulating activities associated with fight or flight. The PSNS and the SNS are complementary with regard to digestion; specifically, the parasympathetic and sympathetic governance of the cephalic phase of digestion.

Sensory Receptor Cells

Our senses can gather 11 million bits of information per second, more or less subjectively. These vast amounts of data are encoded, compressed (package), and transmitted to the brain in a tenth of a second. The ability to perceive and discern visually with our eyes, the ability to recognize and distinguish scents and odors with our nose, and the ability to experience the sensations of various flavors with our tongue are possible by sensory receptor cells (SRC) whose functions are to detect stimuli (changes) to our external and internal environment, and electrochemically transmit the sensory stimulated information to the nervous system.

• Sensory receptor cells/nerve fibers vary in diameter, function, cell body type, and in length (< less than 1 millimeter and up to 1 meter (3 feet) or more >). 

• Several-thousand sensory nerve fibers (more or less) are bundled together into one fascicle; there are multiple fascicles within one sensory receptor nerve; and each fiber, fascicle, and nerve is encased by a layer of connective tissue that varies in density.

In essence there are millions of sensory receptor cells/fibers in one single sensory receptor nerve making them ultra - hyper - sensitive to their respective stimuli, and ultra-hyper fast at transmitting stimuli.

Neurotransmitters (NT)

Neurotransmitters (NT) are endogenous substances (chemicals) that are made in the cell body of the neuron and stored in synaptic vesicles.  Upon stimulation, nerve impulses send the synaptic vesicle down the axon of the nerve fiber to the presynaptic axonal nerve terminal into the synaptic cleft where the NTs bind with the receptors present in the postsynaptic membrane of another neuron (or muscle fiber).

The action that follows activation of a receptor site may be either depolarization (an excitatory postsynaptic potential) or hyper-polarization (an inhibitory postsynaptic potential). A depolarization makes it more likely that an action potential will fire; a hyper-polarization makes it less likely that an action potential will fire.

Thought and Memory 

The Limbic System operates by influencing the endocrine system and autonomic nervous system, and is the central terminal of our emotions.  The limbic system is responsible for learning, and is critical in the formation of new memories because it combines higher mental functions and primitive emotion into one system that supports behavior, motivation, long term memory, and olfaction.

There are immense data inputs from afferent (sensory) neurons from cortical areas, sub cortical areas, and diencephalic structures that interact with the limbic system.

The limbic system is the reason why physical things like eating are very pleasurable: the dorsolateral prefrontal area searches memory for relevant experiences and also stores working memory, and the orbitofrontal region manages emotional impulses.

Declarative memories are comprised of conscious recollection of factual information, and episodic memory (autobiographical memories), requires neural processing in the hippocampus.

• Hippocampal neural processing can regulate the consolidation of food-related declarative memories; 

• Declarative memories of previous meals or eating occasions can be consolidated and retrieved at a later time to influence subsequent feeding behaviors.

• In addition to circadian entrainment cues, exposure to sensory related food cues (e.g., orosensory, visual) and cognitive factors (e.g., thinking about food) can generate cephalic-phase responses (discussed below).

Smell (Olfaction)

When we inhale airborne molecules through our nose (olfaction), the odorant molecules dissolve into the mucus that lines the superior nasal cavity and binds the odorant molecules to protein receptors on specific cilia connected to olfactory dendrites buried in the apical surface of the olfactory epithelium. 

The chemical odorant stimulates a graded membrane potential which triggers a series of nerve impulses that transmit information about the odor to the brain along the olfactory tract (a group of axons within the olfactory nerve that connects to the olfactory bulb on the ventral surface of the temporal lobe. 

Axons split off and travel to the cerebrum, primary olfactory cortex of the temporal lobe; other axons project to structures in the limbic system and hypothalamus where smells become associated with long term memory and emotional responses.  The olfactory system and cerebral cortex share and an intimate connection where sensory memory and emotions are triggered by certain odorants.

Taste (Gustation) 

There are four types of raised bumps (papillae) on the surface of the tongue: circumvallate, foliate, filiform, and fungiform; and within these papillae are taste buds that contain specialized receptor cells for the gustatory transduction of taste stimuli.

The receptor cells are sensitive to the chemicals in the food we ingest; and based on the amount of chemical stimulation, gustatory cells will release neurotransmitters onto the dendrites of sensory neurons; taste cells synapse with primary sensory axons and the pathway is via the vagus, glossopharyngeal, and facial nerves. 

The vagus nerve connects to to taste buds from the posterior tongue, and pharynx.  The glossopharyngeal nerve connects to taste buds in the posterior 2/3rds of the tongue; and the facial nerve connects to the anterior 1/3rd of the tongue. (image of connections)

Sight (Visual)  

The sight of food enters the eye and the refracted image hits the retina where large amounts of photoreceptive cells (rods and cones) detect photons of light and transduces the image into neuronal signals aka nerve impulses that are transmitted along the optic nerve of each eye. 

Both optic nerves meet at the optic chiasm at the base of the hypothalamus of the brain where the visual information from both eyes are combined, and then spilts according to each visual field.  The right and left visual fields of view each travel on their own optic tract which terminate in the Lateral Geniculate Nucleus (LGN) which is a relay center in the dorsal part of the thalamus.

Neurons from LGN send around 90% of their axons through optic radiation, a direct pathway to the primary visual cortex of the occipital lobe, and the other LGN axons stimulate the cerebral cortex where neurogenic signals co-initiate the cephalic phase of digestion via the hypothalamus, and down to the medulla.

Pathways of Innervation

The pathway of innervation depends on the sense stimulated, our state of being at the time of stimulus, and our declarative and episodic memories of the stimulation.  

The Facial Nerve - (Cranial Nerve VII - CN VII) is a mixed nerve consisting of both preganglionic sensory and motor nerve fibers that provide important parasympathetic regulatory control over salivation. CN VII originates in the Superior Salivatory Nucleus (SSN) of the brain stem.

The Superior Salivatory Nucleus (SSN) of the facial nerve is a visceromotor cranial nerve nucleus located in the pontine tegmentum of the brain stem; it is one of the salivatory nuclei. The SSN innervates preganglionic CN VII at the submandibular ganglion, which supplies the submandibular and sublingual glands.

• the superior salivatory nucleus (parasympathetic) gives rise to general visceral efferent (GVE) fibers of the facial nerve.

• the solitary tract nucleus or nucleus of the solitary tract nuclear complex (sensory), which is responsible for taste sensation transmitted via special visceral afferent (SVE) fibers of the facial nerve.

• the (2) chorda tympani is a branch of the facial nerve carrying sensory and parasympathetic preganglionic fibers. The afferent special (gustatory) fibers of the chorda tympani transmit the taste sensations from the lingual papillae of the anterior two-thirds of the tongue via the lingual nerve, while the efferent parasympathetic preganglionic fibers synapse in the submandibular ganglion to provide secretomotor innervation to the submandibular and sublingual glands.

• the Gustatory System (GS) also controls the volume of saliva secreted; it’s dependent on perception of taste-intensity (bitter, sweet, sour, umami), and smell (olfaction). Other salivary stimuli are chemosensory, masticatory or tactile.

The Glossopharyngeal Nerve - (Cranial Nerve CN IX) is a mixed nerve consisting of both preganglionic sensory and motor nerve fibers that provide important parasympathetic regulatory control over salivation.  CN IX originates from the Inferior Salivatory Nucleus (ISN) of the brain stem.

The Inferior Salivatory Nucleus (ISN)

• General Visceral Efferent (GVE): preganglionic motor nerve fibers; (3) provides the parasympathetic innervation component of glossopharyngeal nerve (CN IX) to the Otic Ganglion where they synapse, and postganglionic fibers from the otic ganglion then provide input to the parotid gland.

Afferent signaling arises from gustation, olfaction, visualization, mastication and memory, and is modified by signaling from other centers in the central nervous system before efferent signals are delivered to salivary glands in autonomic nerves. 

Autonomic Salivary Stimulation and Control

Salivation is critically important to the initial pre-digestive phase of the digestion process; it prepares food for swallowing, aids in speaking, and contains mediators and immunoglobulins that provide an initial protective barrier against potentially dangerous organisms that gain access to the oral cavity.

Salivary glands have both sympathetic and parasympathetic innervations, their respective functions are typically opposite of each other; yet complimentary to one another.

The secretion of saliva occurs by the energy consuming active two-stage process of stimulus secretion coupling.  These events involve the release of neurotransmitters from vesicles in nerve terminals adjacent to parenchymal cells which stimulate them to discharge secretory granules, water and electrolytes as well as contraction of myoepithelial cells.

The secretion of salivary fluid and proteins is controlled by autonomic nerves. All salivary glands are supplied by cholinergic parasympathetic nerves which release acetylcholine that binds to M3 and (to a lesser extent) M1 muscarinic receptors, evoking the secretion of saliva by acinar cells in the end pieces of the salivary gland ductal tree.  

This parasympathetic outflow is coordinated through the medulla, and innervation occurs through both the facial and glossopharyngeal nerves. Afferent information from the mouth, tongue, nose and conditioned reflexes are integrated within the brain, and in the presence of food, parasympathetic stimulation evokes a copious flow of saliva when acetylcholine (ACh) is released onto M3 muscarinic receptors that effects: 

• Salivary acinar cells to increase secretion of saliva

• Duct cells to increase HCO3– secretion

• Co-transmitters result in increased blood flow to the salivary glands

• Contraction of myoepithelium to increase the rate of expulsion of saliva

The Sympathetic Outflow - Most salivary glands also receive a variable innervation from sympathetic stimulation via the superior cervical ganglion which release noradrenaline and acts upon alpha and beta adrenergic receptors,  resulting in:

• Decreased production of saliva by acinar cells and also ductal cells

• Activates contraction of the myoepithelial cells of the salivary ducts

• Decreased blood flow to the glands 

• Increased protein secretion 

• The protein content of saliva is additionally dependent upon signaling by neuropeptides in the major salivary glands (parotid, submandibular and sublingual), by sympathetic nerves and the release of noradrenaline.

Salivary Glands

There are three pairs of major glands and numerous minor salivary glands located in the oral cavity. The parotid, submandibular, and sublingual salivary glands are made of secretory units called acini that are comprised of serous and mucous acinar cells. 

The 3 major salivary glands contribute to 90% of total saliva secretions, while minor salivary glands contribute to the remaining 10%. The amount of saliva secreted by the major and minor glands is referred to as whole saliva. 

The acini are connected to salivary ducts, and the acinar cells are surrounded by myoepithelial cells or basket cells which are contractile cells responsible for the flow of secretions of saliva by contraction. 

Salivary gland acinar cells are chloride and sodium secreting, and the isotonic fluid produced is rendered hypotonic by salivary gland duct cells and this bicarbonate-rich fluid containing digestive enzymes and protective proteins and other components flows into the lumen of the mouth.

The mechanical process of disintegration mastication, mixing, churning, grinding in the mouth with the teeth, tongue, and salivary glands facilitates the action of saliva and its constituents onto the food.

Constituents of Saliva

• water

• electrolytes - sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate, and iodine; all contribute to the ionic strength, serve as buffers, and maintain a slightly acidic pH for oral health.

• antimicrobial agents - oral gatekeepers are the first line of defense against: 

  • bacterial, fungal, and viral antigens.

• salivary enzymes - control the food for digestion with two groups of enzymes: 

  • lingual lipases: fat-decomposing ‘lipolytic’ enzymes 

• salivary amylases: carbohydrate-decomposing ‘amylolytic’ enzymes

This enzymatic transformation starts in the mouth, while their secretion starts at the thought, smell, sight and/or memory of the food.  This -psycho neuro humoral connection- to salivary enzyme secretion, regulation, and activity is tightly regulated, and maintained throughout the digestive system by the ANS.

Breaking down food to benefit the body is accomplished by a complex system of sensory receptor cells, nerves, chemicals, hormones, and enzymes.  Neurotransmitters and hormones signal the body as to what enzymes are needed and when they are needed to do the work; these enzymes then become the molecules that perform the biological task of enzymatic-hydrolysis.

Once these macro-structures have been physically broken down and enzymatically hydrolyzed into smaller molecules they are then ready to be swallowed and further worked upon by the gastric juices and peristalsis of the stomach.