Physiology Module 3 - The Peripheral Nervous System

Queen's University Physiology 215 Module 3

Threshold

Minimum threshold stimulus before they are activated.

Properties of Receptors - MILD

There different types of stimuli that can initiate transduction and all action potentials are the same, but electrical signals are not. There are four different properties to allow the CNS to accurately differentiate incoming signals from the PNS: Modality, Intensity, Location, Duration

Properties of Receptors: Modality

There are different types of receptors in our body, like photoreceptors, mechanoreceptors, thermoreceptors, chemoreceptors

Properties of Receptors: Intensity

The stronger the stimulus, the more frequent the signal, but amplitude stays the same

Properties of Receptors: Location

The brain is able to identify the site of sensory stimulation using the location of activated afferent fibres.

Receptive Field (Location)

Each neuron has a region of the environment to which is sensitive, i.e. the receptive field. If a stimulus appears in a neuron's receptive field, the neuron will fire and location is communicated to the brain.

Multiple Sensors (Location)

Our brain can compare inputs from more than one sensor. For example, we have two eyes and two ears

Gradients (Location)

With smell, we can determine location based on gradients. For example, if we smell something and then move in some direction, if the smell becomes more intense, we know we are going towards its source

Duration

Afferent neurons can encode duration of the stimulus and communicate this to the brain for processing. Some cells fire as long as the stimulus is present, and some fire briefly as the stimulus goes on, then stop, and then fire briefly when the stimulus goes off

Transduction: Receptor Potentials and Generator Potentials

Transduction occurs inside a receptor. Stimulation of the receptors alters the membrane permeability, causing the opening of nonselective cation channels. When cations enter a neuron, they will depolarize the membrane

Receptor Potentials

Change in potential due to an incoming signal

Generator potentials

The transmembrane potential difference produced by activation of a sensory receptor

Graded Potentials

Are not an action potential, but the signal generated by receptor and generator potentials. Amplitude can vary depending on strength and duration of stimulus. Can be EPSPs or IPSPs.

Specialized Afferent Endings

The receptor potential itself can cause the afferent nerve fibre to reach threshold and trigger and action potential

Separate Receptor Cell

• When the receptor potential is strong enough it will release a chemical messenger that diffuses to the afferent neuron and opens chemically gated sodium channels.

• If threshold is achieved, then the afferent fibre will initiate and propagate an action potential

Can Receptors Adapt

Receptors have the ability to regulate their responses and this is called adaptation. A stimulus of a same intensity does not always bring about the same magnitude of receptor potential. Receptors can adapt to the signal by enhancing or lessening their response. There are two different types of receptors that vary in their speed of adaptation

Tonic Receptors

• Generally slow adapting or do not adapt at all. They are important in situations where a near constant signal from a stimulus is necessary.

• Example: Muscle stretch receptors as the CNS constantly requires knowledge of the state of contraction of all skeletal muscles in order to maintain posture and balance

• Similarly, pain receptors are tonic receptors as the CNS requires knowledge of painful and potentially dangerous stimuli

Phasic Receptors

• Are rapidly adapting such that upon initiation of a stimulus action potentials are generated.

• However, the receptor will stop generating action potentials rapidly, even in the presence of the stimulus.

• Once the stimulus is removed phasic receptors will again respond will depolarization called an off response. This type of receptor is important for monitoring changes in stimulus intensity

Nociceptor Modalities

• Mechanical nociceptors:

  • Responds to physical damage such as cutting or crushing

• Thermal Nociceptors

  • Respond to temperature, especially heat

• Chemical nociceptors: Respond to noxious chemicals which are both external and internal to the body

Nociceptors

Are specialized nerve endings of afferent nerve fibres called pain fibres.Pain be categorized into fast and slow, based on conduction speed

A-delta fibres (Fast Pain Fibres)

They are responsible for responding to temperature, and both chemical and mechanical stimuli. The perceived sensation associated with activation of these fibres includes acute, sharp, or stabbing pain. Faster conduction speed is due to diameter of myelinated cells which are larger.

C-Fibres (Slow Pain Fibres)

They are unmyelinated, and similar to fast pain fibres (A-delta).They are responsible for responding to both chemical and mechanical stimuli as well as temperature. However, unlike A-delta fibres, polymodal receptors (Receptors that can respond to more than stimuli) can be activated. The perceived sensation associated with activation of these fibres includes burning, aching, or throbbing

Bradykinin

 a chemical that is activated by enzymes that are released from damaged cells. Once activated, bradykinin can directly stimulate nociceptors. As there are no adaptation to the stimulus, the nociceptors are stimulated until the bradykinin is removed, which could explain long lasting, persistent pain

How does our brain process pain?

When an action potential reaches the end of an afferent pain axon, it triggers the release of neurotransmitters. The most well studied are substance P and glutamate. Substance P coexists with glutamate to activate the ascending pathways and transmit the pain signals to higher levels for further processing

Regions involved in Pain Processing

• Hypothalamus/ Limbic System

  • Receives input from the thalamus and reticular formation, and allows for behavioural and emotional responses to the pain stimuli

• Cortex

  • Cortical somatosensory processing localizes the pain to a discrete body region

• Thalamus

  • Processing here allows for the perception of pain

• Reticular Formation

  • Increases the level of alertness and awareness of a painful stimulus

Glutamate

An amino acid that also functions as a neurotransmitter. It is released by nociceptive afferent nerve fibres to activate the postsynaptic glutamate receptors on neurons in the dorsal horn of the spinal cord. Glutamate has two actoins that depend on the type of receptor on the dorsal horn neurons that are activated: AMPA and NMDA

AMPA receptors

• Activation of AMPA receptors lead to permeability changes that can generate action potentials in the dorsal horn neuron and send the signal to higher brain centres

• As sodium enters the AMPA channel, depolarization occurs.

• Only when a certain level of depolarization is reached will the Mg2+ ion in the NMDA channel be dislodged, and the NMDA channel will be activated

NMDA Receptors

• Once NMDA receptors are activated, they allow calcium to enter the neuron.

  • Leads to the activation of a second messenger pathway that results in the neuron being more excitable than normal

  • Explains why injured areas are more sensitive to stimuli that would normally not cause pain

  • When I rub my clothes against an area with sunburn

 

How are pain signals stopped?

Pain afferent fibres do not adapt. When a painful stimulus is initiated, there is decrease, but not because of adaptation. It is the result of the CNS's built-in pain suppressing system, such as endogenous opiates.

Endogenous Opiates

 (Substances that are produced by the body and have pain killing effects (endorphins, enkephalins, dynorphins) that act on opiate receptors and result in suppression of neurotransmitters being released from the afferent pain fibres.

Exogenous Opioids

 (Substances that are not produced by the body and have painkilling effects (morphine) can activate the opioid receptors to decrease perception of pain)

Iris

The coloured part of the eye

Pupil

allows light to enter into the eye

Pupillary Constriction

Caused by parasympathetic stimulation. A set of muscle is organiced in a circular fashion around the pupil and the muscles constrict to make the pupil smaller

Pupillary Dilation

Caused by sympathetic stimulation. One set of muscles organized in a radial fashion (from pupil to edge of iris), and these muscles contract to dilate the pupil to allow for more light

Light Rays

Made up of photons that travel in waves. Waves can vary in wavelength and intensity (height). Lightwaves need to be bend so that they can enter the eye and allow the eye to focus it for further processing. The eye has refractive structures that allow for processing of light

Corena

The outer layer of the eye that refracts light. Contributes to the refractive ability of the eye because of the large density difference at the air-cornea boundary. Refractive ability of the eye remains constant as the curve of the cornea cannot be altered. In some people, the surface of the cornea is uneven, which results in uneven refraction of light known as astigmatism

Lens

Located behind the pupil. Because of its shape, it has the ability to further light rays on the retina. The goal of lens is to focus light rays onto the retina to convert the light energy into electrical signals sent to the CNS.

Accommodation of Lens

Is the eye's ability to adjust the lens to maintain focus on something. It is controlled by the ciliary muscle and suspensory ligaments. When the muscle contracts, it reduces the tension of the ligaments and the lens becomes more convex

Ciliary muscle contraction is also under control of the ANS, with sympathetic stimulation causing relaxing and parasympathetic stimulation causing contraction

Distant Light Source

When the light sources is more than 6 meters away from the lens, the light rays are parallel to one another when they enter the eye

Near Light Source

When the light source is closer than 6 meters to the lens, the light rays are diverging (moving apart from each other) when they enter the eye. In these situations the eye accommodates by changing the shape of the lens so that it has a greater ability to bend light, allowing the eye to focus on the image

Near sightedness

In near sightedness, your eyeball is often too long for the light to reach the retina

Far-Sightedness

your eyeball is too short and the focus of the eye reaches beyond the retina

Retina

Extension of CNS. Each one has over one million nerve fibres bringing information to the brain (makes sense since we use our eyes 24/7 almost) The structure of the retina is complex and has many layers. Can divide into three layers of excitable cells, the photoreceptor, bipolar, and ganglion cells.

Rods and Cones

Rods help us see dark light, Cones help us see color. The photoreceptors in our body to process light.

Bipolar Cells

The middle layer of bipolar cells are involved in the transmission of signals from the rods and cones to the ganglion cells

Ganglion cells

The neurons located at the inner surface of the retina. Axons of the ganglion cells make up the optic nerve

Accommodation of Retina

• The retina is continuous throughout the entire inner surface of the eye with the expectation of the optic disc, where the ganglion cell axons bundle together to form the optic nerves (just one per retina)

• Because this region has no rods and cones, it creates a blind spot in the eye. Higher visual processing fills in this blind spot

Central Processing of Vision

• Information from the optic nerves is transmuted to the visual pathway in the thalamus. The thalamus does initial processing by separating different visual stimuli (colour, form, depth, movement, etc.) and relaying each to different zones in the cortex.

• The visual cortex is organized into functional columns with alternating columns devoted to the left and right eyes. The brain can compare these neighbouring columns to allow depth perception and allow you to estimate distance

• Vision takes up a lot of cortex processing, which is about 30% of the cortex capacity

Visual Processing

• Visual processing is not as simple as receiving the information from an eye. We have two eyes that are set apart, and because they are set apart, they receive different visual input and send different information to the brain.

• Having two eyes improves depth perception, which is lost if a person loses their sigh in one eye

The Visual Pathway

• Vision on the right visual field is processed on the left side of the brain, and vision on the left visual field is processed in the right side of the brain

Pitch

Determined by frequency of vibrations. How low and high the note is.

Intensity (loudness)

Determined by amplitude of sound waves.

Timbre

• The quality of a sound is the overtones that are superimposed on the pitch.

•  It allows a person to locate the source of the sound as each source produces a different pattern of overtones.

• Timbre allows us to distinguish between voices and instruments even if they are creating the same tone with the same loudness

External Ear: Pinna

• The external skin covered cartilage the collects the sound waves.

• Is essential for location of sound.

• Our two ears allow for the precise pinpointing of sounds wen combined with the ability to move the head to optimize locomotion

Ear Canal

• Conducts the sound waves towards the tympanic membrane. The entrance to the ear canal is guarded by fine hairs and special cells that secrete earwax.

• The earwax and hair prevent airborne particles from entering the ear canal, and have properties which aid in the defence against bacteria by making the environment more acidic

Tympanic Membrane

• Stretches across the entrance to the middle ear.

• Vibrates when hit by incoming sound waves

• For the membrane to vibrate efficiently, the air pressure on either side needs to be similar as the middle ear cavity is connected to the pharynx via the eustachian tube, the pressure in the middle ear equalizes with the atmospheric pressure

Middle Ear: three bones

Malleus incus, and stapes.  transfer the movement of the tympanic membrane and amplify the sound as it is transmitted to the fluid of the inner ear. Tympanic membrane, to the malleus, incus, and then stapes

Vestibular Apparatus

• Provide information essential for equilibrium and coordination of movement by detecting changes in head movement. Similar to the cochlea, the vestibular apparatus is fluid filled and contains sensory hair cells that are triggered by movement of the fluid

• Neuronal signals initiated in the vestibular apparatus do not reach conscious awareness. However, some people have a very sensitive vestibular apparatus that causes them to feel the dizziness and nausea that we call motion sickness

Equilibrium

• Signals from the vestibular apparatus are sent to the vestibular nuclei in the brainstem and to the cerebellum

• The vestibular information is integrated with the rest of the afferent signals from the skin, eyes, muscles, and joints to:

  • Maintain balance and posture

  • Allow the eyes to remain fixed when turning the head

  • Perceive motion and orientation

Chemoreceptors

Relies on chemicals that bind to these receptors. Used in taste and smell sensations.

Tongue

Where the chemoreceptors for taste are housed. Are organized into taste buds

Taste buds

• The tongue is covered with thousands of small bump called papillae. Within each papilla are hundreds of taste buds.

• Taste buds are the cluster nerve endings on the tongue and in the lining of the mouth that provide the sense of taste

• Each taste bud is made up of about 50 receptor cells and supporting cells.

• Each bud has a small opening that allows fluids to come into contact with the taste with the taste receptors

• Unlike vision or hearing receptors, taste buds have a limited lifespan with a turnover of around 10 days after which they are renewed

Taste Receptor Cells

When a tastant binds to its receptor, ion channels create a depolarizing potential. This depolarizing potential can initiate an action potential in the nerve endings of afferent neurons

Afferent Neurons in Taste

Afferent neurons associated with taste buds send their signals to the brainstem and thalamus before going to the cortical gustatory area, a region in the parietal lobe adjacent to the tongue area of the somatosensory cortex. From the brainstem, some signals go to the limbic systems to be able to distinguish between pleasant and unpleasant as well as trigger any associated behavioural responses

Salty Taste

Salty taste cells are stimulated by salts such as NaCl. Taste cells for salt have specialized Na channels that allow for the direct entry of Na that can depolarize cells

Sour Taste

Sour taste cells are stimulated by acids. The free H+ of acids blocks K+ channels in these cells, which reduces the outward flow of K+ and thus can produce a depolarizing channel

Sweet Taste

• Sweet taste cells are stimulated by glucose. Binding of glucose activates a G protein and generates cAMP that ultimately can inhibit certain K+ channels to produce a depolarizing potential.

• Artificial sweeteners are designed to interact with sweet taste cells but contain no calories as they cannot be used to produce ATP

Bitter

• Are more diverse and stimulated by a wide variety of compounds such as alkaloids (caffeine, nicotine, morphine, strychnine, and other toxic plant metabolites)

• Most poisonous compounds have a bitter taste which suggest that this type of receptor is involved in a protective mechanism

• Mechanism of action is similar to sweet cells

Umami

• These taste cells are triggered by amino acids such as glutamate. The precise cellular mechanisms of umami receptors do involve G proteins but the second messenger pathways are relatively unknown.
  Because this type of receptor senses protein rich foods they are the receptors for meaty flavours

Olfactory Receptors

•  The chemoreceptors for smell are in the top of the nasal cavity, as shown in the image.

• Olfactory mucosa is a small patch of skin located In the ceiling of the nasal cavity and contains the olfactory receptor cell as well as two other types of cells:

  • The supporting cells that secrete mucous

  • Basal cells that are the precursor for new olfactory receptor cell. These cells have a lifespan of about two months

Process of Olfaction

• Chemicals that can be 'smelled' dissolve in the mucous layer and interact with cilia on the olfactory receptor cells

• Binding of an odorant activates G proteins and mobilizes the second messenger cAMP that leads to the opening of Na channels to initiate a depolarizing receptor potential and subsequent action potential in the afferent fibre

• There are five million olfactory receptors in the human nose that can be divided into over a thousand types

• This allows different odorants to be able to activate several receptors to create distinct and complex smells.

Sympathetic Nervous System (SNS)

• The primary role is to stimulate flight or fight response

  • A physiological reaction in response to a perceived harmful event, attack, or threat to survival

• During their response, the adrenal medulla produces hormones epinephrine and norepinephrine

Parasympathetic Nervous System

Mainly responsible for rest and digest. Includes process that happen when the body is at rest, like digestion, urination, and salivation

Autonomic Nerve Pathway

• All ANS pathways involve a two neuron chain connecting the CNS to the effector. The cell body of the first neuron is located within the CNS and its axon, called the preganglionic fibre, synapses with the cell body of the second neuron

• The second neuron's cell body is located within a cluster of neuronal cells called a ganglion. The axon of the second neuron, called the postganglionic fibre, innervates the effector organ

Autonomic Nerve Origin

In the ANS, the SNS and PNS have different origins.

Sympathetic Fibres

• The fibres here originate in the thoracic in lumbar regions of the spinal cord

• Preganglionic fibres tend to be short and terminate in ganglia located in chains down both sides of the spinal cord

• Their long postganglionic fibres terminate on the effector organs. Some preganglionic fibres, however, actually pass right through the ganglia and terminate in ganglia (collateral ganglia) that are located roughly halfway between the CNS and the effector organs

• Uses epi and NE at the postgangionic end, and are adrenergic fibres

Parasympathetic

• Preganglionic fibres arise from the brain or lower spinal cord. The preganglionic fibres are long and terminate in ganglia located close to the effector organ

• The postganglionic fibres are very short

• Uses Ach at the postganglionic end, and are called cholingeric fibres

Autonomic Regulation

• All effector organs receive input from the PNS and SNS systems - a concept referred to as dual innervation

• Some organs like kidneys and adrenal glands to not have direct innervation to both systems

• Most afferent nerve traffic from the visceral organs and visceral activities such as digestion, sweating, and circulation never reach the level of consciousness and are regulated by autonomic efferent output

Autonomic Innervation of Organs

• Sympathetic system is excitatory

• Parasympathetic system is inhibitory

  • SNS increases heart rate, while PNS decreases it for example

• There are examples where this is the opposite

  • Digestive system: SNS decreases gastric motility and PNS increases it

• Main takeaway: Both systems have opposite regulatory actions. This is essential as it allows precise regulation of homeostatic parameters

Sympathetic and Parasympathetic Tone

• Relative contributions are called sympathetic tone or parasympathetic tone

• When one of these symptoms gets activated more than this tonic activity, the other system tends to decrease firing so one systems becomes the dominant influence on the organ

Sympathetic Dominance

When flight or fight systems are activated, sympathetic dominance occurs. Examples: Heart rate and pressure goes up, so your arteries increases blood pressure through contraction. Dilating respiratory airways to bring more oxygen. Breaking down glycogen stores and glucose and fats maybe for energy use. Etc.

Parasympathetic Dominance

Is active during times of rest. Lets say in the example above we have been running away from the bear. Once the bear is gone, our PNS begins relaxing and calming the body so It can recover from the effects of your SNS. Digestion would continue, renal functions are also normal, less sweating, lowered heart rates through vasodilation, etc.

Dual Innervation Exceptions

• Most arteries and veins receive SNS only and their regulation is achieved only and regulation is achieved through decreasing the SNS

• The only blood vessels that have dual innervation are found in the penis and clitoris

• Most sweat glands receive sympathetic innervation. The sympathetic postganglionic fibres release Ach instead of norepinephrine

• Salivary glands receive dual innervation, but both systems can stimulate salivary secretion

What do the adrenal glands do in the ANS?

• Adrenal medulla functions like a sympathetic ganglia in that it is innervated by a sympathetic preganglionic fibre, but does not give rise to a postganglionic fibre

• Upon SNS, the adrenal medulla releases chemical transmitters into the blood.

• The transmitters qualify as hormones since they are released into the circulation

• 20% of these are norepinephrine (associated with sympathetic postganglionic fibres) and 80% epinephrine, a closely related compound

• Upon SNS, the adrenal medulla acts as a global amplifier of the SNS

Receptors of the ANS

• There are different types of receptors on an organ.

• Ach, norepinephrine, and epinephrine are they neurotransmitters, it is the receptors of these chemicals that defines how tissues will respond to ANS stimulation.

Cholinergic Receptor: Muscarinic

Responds to acetylcholine from the PNS postganglionic fibres. Found on the effector cell membranes. Binding of Ach or muscarine to these receptors trigger a G-protein coupled reaction that results in the opening of cation channel. Creates a depolarization potential

Cholinergic Receptor: Nicotinic Receptors

Found on cell bodies of postganglionic cells in autonomic ganglia and bind Ach released from both sympathetic and parasympathetic fibres. Binding of Ach or nicotine to nicotinic receptors leads to opening of the channel, leading to response

Adrenergic Receptor

A G-protein coupled receptor in the membrane of cells that responds to catecholamine (aromatic amines) neurotransmitters (E and NE). These will truly define how tissue or organs will respond to SNS. Can be classified as alpha or beta receptors and then further subclassified as alpha 1, alpha 2, or beta 1 and beta 2.

Alpha Receptors

Both a1 and a2 receptors have a greater sensitivity to norepinephrine than epinephrine. All adrenergic receptors activate G-proteins. a2 activation suppresses the cAMP pathway while a1 activates the Ca2 second messenger system

Beta Receptors

• B2 receptors have a greater affinity for epinephrine than B1 receptors.

• B1 receptors respond equally to norepinephrine and epinephrine.

• All adrenergic receptors activate G-proteins

• Beta 1 and beta 2 enhance the cAMP pathways

Tissue Selective Responses

• Effects of SNS is determined by the number and type of adrenergic receptors in the target tissues and organs

• Example: A1 receptors are almost always excitatory and because they are expressed in smooth muscle cells of blood vessels, their stimulation causes contraction

• In contrast, the smooth muscle cells of the digestive system primarily express a2 receptors, which when activated causes a decrease in contraction

• Stimulation of b1 receptors is also excitatory and are normally found on the heart, where as B2 is inhibitory and are found in the smooth muscle cells of arterioles and the respiratory airway

a1 Receptors

are almost always excitatory and because they are expressed in smooth muscle cells of blood vessels, their stimulation causes contraction

a2 Receptors

• the smooth muscle cells of the digestive system primarily express a2 receptors, which when activated causes a decrease in contraction