Neuroaesthetics, Lecture 2
The macro anatomy of the brain
So far, we have not focused on the anatomy of the brain and the nerve cells. (next) On the macro-anatomical level, the brain consists of two hemispheres containing the same anatomical structures. Nevertheless, the two hemispheres are far from identical physiologically. For instance, the main language areas are localized in the left hemisphere. The brain, which you can see here, is seen from behind, toward the protruding occipital lobes, where the visual cortex is localized.
We see that the brain is strongly folded. This is a characteristic of the brains of advanced Mammalia, and, particularly of primates: that is the apes and the humans. The folding of cortex is the only way to keep with the fact that complex cognition requires large areas of cortex, 1.350 ccm in humans, the volume of our scull. The folding organizes the brain surface into gyri, which is plural for gyrus, and sulci, plural for sulcus, where the gyri is mounting on the surface, and the sulci are the grooves between them (next)
When the early anatomists dissected the brain they found that the outer surface was gray, covering an inner, so called white substance. We still use the words white and gray substance to designate the two layers. The white substance is white because it consists of large bundles of nerve fibers, where most of the fibers are encapsulated in so called neuroglia, cells that are wrapped around each nerve fiber, and, hence, provide them with an insulating layer of fat.
Gray substance is grey because it consists of the so called nerve cell bodies, the genetic and ´administative` area of the cell. (next) The gray substance is found in the cortical areas of the brain. (next)
Bundles (next) of nerve fibers cross from one hemisphere to the other through the so-called commissures. In this slide, you can see the large nerve tract, the corpus callosum, which means “hard body”, and the anterior commissure. The crossing fibers connect corresponding gray substance areas in the two hemispheres.
We will take a closer look at the (next) macro anatomy of the brain.
The (next) most conspicuous sulci divide the brain into separate lobes. (next) We have the frontal lobe, the parietal lobe, the occipital lobe, and the temporal lobe, with their respective cortical and sub-cortical structures. The central sulcus separates (next) the somatosensory areas in the postcentral gyrus from the motor areas in (next) the precentral gyrus. The somatosensory cortex receives information from our senses, while the motor areas are controlling our muscles.
A few word has to be said about function already at this early stage in my lecture, to give some keys for the rest of my presentation: (next) In the frontal lobe we find many higher order cognitive processes, among which are decision making, moral judgments, making choices within social settings etc. (next) The parietal cortex is a cortex for conception of 3D, perspective, and symmetry. (next) In the occipital lobe we find our primary visual areas; and (next) in the temporal lobe are areas for hearing, for word conception, cortex for smell, as well as areas that are located deep in the temporal lobe and whose function are connected with the emotional network, or limbic system, as well as memory etc. We will return to some particular areas for deeper analysis of function.
Before we go on to details, we need to consider some terminology for navigating among the brain structures (next):
anterior – posterior
rostral – caudal
lateral – medial
superior – inferior
On (next) the present slide we see the different sensory inputs to the brain, and the motor output: We have the somatosensory inputs from the different sense organs of our skin ending in the somatosensory cortex located posterior to the central sulcus; we have the visual input to the primary visual cortex in the occipital lobe; the auditory inputs terminate in the temporal lobe; the olfactory stimuli trigger activation in the medial part of temporal lobe, while the gustatory fibers, those carrying taste signals, terminate in the primary gustatory cortex. (next) It is located in the insular area (insula and the frontal operculum on the inferior frontal gyrus of the frontal lobe).
Finally, we have the motor cortex, from which the motoric signals run through the motoric nerves down the spinal cord, where they are connected to a second set of neurons, which lead to those muscles that are under our conscious control (next).
The somatosensory and the motoric cortices are located on each side of the (next) central sulcus; the motor cortex anterior to the central sulcus and the somatosensory posterior to it. (next) This slide shows area in the motor and somatosensory cortices concerned with particular areas of the body.
The reason why the head and the arm, the tongue and the swallowing apparatus occupy a larger part of the cortices is that a much greater control is required, for instance, to move our fingers than our toes;
mind, … how would you react to a dentist controlling the drill with his feet?
The cerebral cortex has been investigated (next) in microscopic details by Korbinian Brodmann (1909/60). He studied every patch of cortex in the microscope. His interest in cell morphology and cytoarchitecture, that is: how cells are arranged with respect to each other within an area resulted in a division of the brain into 52 regions.
In Brodmann’s system the somatosensory areas (next) has numbers 3, 1, and 2, while the (next) motor cortex is identical with Brodmann’s area 4.
The (next) descending nerve fibers from the motor cortex cross the midline; they control the contralateral part of the body. The ascending, somatosensory fibers will also cross the midline ascending towards somatosensory cortex on the contralateral side of the brain.
We (next) will leave the somatosensoric and motoric areas, and go to the visual system. (next) Look at this painting by Richard Anuzkiewicz. … Can you see how it almost vibrates before our eyes? But what happens (next) if we convert it into grayscale?
We will try to explain this feature physiologically. First we will take a brief review of the physiology and anatomy of the visual system.
Here (next), we see a tracing of the visual pathways from the eyes to the brain. Nerve fibers from the nasal part of the eye cross the midline in the optic chiasm, entering the thalamus complex in a nucleus called the lateral geniculate nucleus. The fibers from the temporal part of the retina go uncrossed to the lateral geniculate nucleus.
What this implies is that information from the right visual field projects to the left side of the brain, while information from left visual field is sent to the right half of the brain.
From the lateral geniculate nucleus, the information is sent, by a second set of neurons, to the primary visual cortex in the (next) occipital lobe, also called visual area 1, or simply V1, with the number 17 in Brodmann’s system (BA 17, V1). Let us now take a look at an interesting artwork, (next) Eduard Monet’s Soleil levant, the Sunrise, from 1872, and we will now use this artwork to demonstrate how our brain deals with visual input.
In the grayscale version of Monet’s Soleil levant (1872) the intensely bright sun has almost disappeared. Why?
This is because this sun has the same light intensity, or luminance, as the background colour. But why is the sun so intensely shimmering when we look at the original painting?
The reason is that there are two different systems leading from the primary visual cortex to higher visual areas of the brain. The «where system» which follows the bundle of nerve fibers called the (next) (next) superior longitudinal fasciculus is colour blind and tuned to luminance contrasts.
The ventral «what system» follows the (next) inferior longitudinal fasciculus. It is colour sensitive, and have particular centers for recognizing objects, faces etc. The colour sensitive «what» pathway recognizes the sun and its colour in Monet’s painting. The «where» pathway is, however, blind for the isoluminant sun (no luminance contrast between sun and background). This leads to an oscillation between the «what» and the «where» system, which results in a shimmering of the sun. (next)
And it is precisely the same effect that is at work when we look at (next) Richard Anuzkiewicz’ Plus reversed (1960), with its vibrating red and green patches.
(next) Brodmann based his system on micro anatomical details, which shows that one part of the cortex differs from neighboring areas. This lead to different numbers for different cortical areas. The primary visual areas is thus divided in visual 1 and 2, or simply V1 and V2, corresponding to BA 17 and 18. The cytoarchitecture (how the cells are organized) manifests in a distinct stripe in striate cortex (BA 17) while absent in the extrastriatal (BA 18).
Let (next) us move on to the parietal cortex, in which Brodmann’s area 7 occupies a substantial part. The parietal lobe includes neural networks for complex recognition of form, such as 3D; also the brain’s symmetry network is partly localized within the parietal lobe, and partly in the occipital lobe.
Moreover, there is a network of mirror neurons (cf. Lecture 1) in the inferior parietal cortex. When we, for instance, are looking at a sculpture, the mirror neurons will mirror the intended movement of the sculpture. This means that the parietal cortex understands not only the three dimensionality of the form but even the (intended) movement of it. This plays a fundamental role in visuomotor transformation, and spatial recognition processing.
When we try to grasp a 3D form, there will be an activation of (next) BA 7 in the parietal cortex. This means that when we look at sculptures, such as this (next) one by Henry Moore, our (next) parietal lobe both mirrors its movements, and tries to interpret its depth for us, so that we can calculate how it is sculptured around, also at the side that is obscured from our present position.
Experimentally, (next) it has been proved that when we analyze a 3D form, comparing it with another 3D form, trying to find out whether the two forms are equal, a process called mental rotation, the foremost activation takes place in the parietal cortex, (next) in BA 7.
There are also some sex-differences here: men are usually cleverer in mental rotation tasks than women. Women, on the other hand, are much cleverer in a verbal description, telling how different items are located in relation to each other etc.
The differences between sexes are usually explained according to the so called hunter gatherer hypothesis: men were out navigating in landscape, hunting, while women were home, gathering berries, fruits, preparing food etc.
Since the pathway that can analyze 3D has evolved after human and chimpanzee lineages diverged, the sex specific characteristics must have evolved during evolution of hominids, i.e. after the splitting of the lineage leading to homo (man) and that leading to Chimpanzee.
Symbolic expression is a hallmark of cognitive evolution. Art is symbolic expression; but the most fantastic symbolic expression in communication between people is the (next) human languages. The process of identifying the parts of the brain that are involved in language expression began in 1861, when Paul Broca, a French neurosurgeon, examined the brain of a recently deceased patient who had an unusual disorder.
Though this patient had been able to understand spoken language and did not have any motor impairments of the mouth or tongue that might have affected his ability to speak, he could neither speak a complete sentence nor express his thoughts in writing. The only articulate sound he could make was the syllable “tan”, which had come to be used as his name.
When Broca, after the death of Tan, (next) autopsied his brain, he found a great lesion in the left inferior frontal cortex.
Subsequently, Broca studied eight other patients, all of whom had similar language deficits along with lesions in their left frontal hemisphere. This led him to make his famous statement that “we speak with the left hemisphere” and to identify, for the first time, the existence of a “language center” in the posterior portion of the frontal lobe of this hemisphere.
Now known as Broca’s area, this was the first area of the brain to be associated with a specific function:language.
(next) Ten years later, Carl Wernicke, a German neurologist, discovered another part of the brain. This area, now called Wernicke’s area is involved in understanding language. It is located in the posterior portion of the left temporal lobe. People who had a lesion at this location could speak, but their speech made no sense.
Neuroscientists now agree that the area running around the lateral sulcus, also known as the Sylvian fissure, in the left hemisphere of the brain, has a neural loop that is involved both in understanding and in producing spoken language. At the frontal end of this loop lies Broca’s area, which is usually associated with the production of language. At the other end, more specifically in the superior posterior temporal lobe, lies Wernicke’s area, which is associated with the processing of words that we hear being spoken, the comprehension of their meaning. A large bundle of nerve fibers called the arcuate fasciculus connects Broca’s area and Wernicke’s area.
Broca’s area, (next) which has number 44 in Brodmann’s system, is also the (next) locus of substantial networks of mirror neurons, those of the ventral premotor cortex.
Last (next) lecture we saw that if we are looking at someone executing a grasping movement, the mirror neurons in our brain will be activated. The same neurons will be activated if we plan to do a corresponding grasping movement.
The asymmetry of the language areas, its lateralization to the left, and its co-localization with the mirror neuron system, has led to some speculation whether the mirror mechanisms are also left lateralized. Recent studies (Aziz-Zadeh et al., 2006) has, however, documented that the mirror neuron system is not lateralized to left hemisphere, and concludes that the mirror neurons in BA 44 cannot be a precursor to the development of lateralized language function in humans.
Still, one can ask whether the mirror system and the language mechanisms are interconnected in some manner. One possibility is that since speech involves specific motoric actions to move the jaws, precise control of such movements might be learned through observation. If this holds true, this may indicate that mirror neurons in Broca’s area aid in acquisition of novel movement patterns required for speech (D. R. Lametti and A.G. Mattar, Mirror Neurons and the Lateralization of Human Language, The Journal of Neuroscience, June 21, 2006, 6666-6667).
Broca’s area is part of the (next) frontal cortex which, as we have seen, is occupied with complex cognitive processes. Neuroaesthetics has been particularly concerned with certain areas of the frontal cortex. Brodmann area 44, with its population of mirror neurons is, of course, such an interesting area.
We will, however, now move to the prefrontal cortex, (next) mainly Brodmann’s area 10.
The (next) famous German neurologist Karl Kleist (1879-1960) who, based on enormous amounts of patient data and post mortem autopsies, labelled a part of the prefrontal cortex the “efficiency of thought”, localised within Brodmann area 10.
The (next) medial part of BA 10 is activated if we make judgments about what is morally good, what function best in social settings.
Thomas (next) Jacobsen’s research group in Leipzig, Germany, carefully designed an experimental paradigm that enabled them to demonstrate that the neural networks for the aesthetic (next) judgment task in fact overlapped with those working during moral and social judgments. The aesthetic judgment is a cognitive process relying on a network of reasoning; this network is localized in the medial prefrontal cortex, within Brodmann’s area 10 ( BA10).
This shows that our brain, in fact, tells us that what is beautiful is also good. This is fascinating, since this was actually a principle for classical aesthetics, as well as aesthetics of the (next) Middle Ages.
The most ventral part of the prefrontal cortex is called the (next) orbitofrontal cortex since it is located above the eyeholes, the orbita. I will soon return to its function, since it is a very central structure in Neuroaesthetics.
The limbic (next) (next) (next) (next) system is the set of brain structures that forms the inner border of the cortex. We also often refer to the limbic system as the limbic ring. The limbic system is phylogenetic older than the so called neocortex; this means that this emotional system antedates the development of hominines. It is also found in primitive animals, mostly as areas for smell and taste. Let us now compare the brains of amphibian, reptiles, primitive Mammalia and Primates.
In (next) modern amphibians, such as frogs, (next) (next) the gray matter is located deep to the brain surface, and consists of the so called basal nuclei (labelled b), the paleocortex (p), and the archicortex (a). (next) In a more progressive stage, such as in reptiles, (see fig. C) the basal nuclei has moved inwards, and are located on the lower, or ventral, side of the brain. (next) In fig. E, you can see a primitive mammalian stage, such as in rats, where the (next) neocortex (labelled n) occupies the superior surface of the brain, separated from the (next) paleocortex by the rhinal fissure. The ventrally located paleopallium becomes a primary olfactory cortex. (next) The archipallium is folded to become the hippocampus. (next) In advanced mammalia (F), like the primates, the neocortex covers almost all the brain surface, and has become strongly folded. (next) Dorso-medially, we can see that the archipallium is folded to become the hippocampus, our primary structure for memory, and also a central structure in our system for emotions.
The limbic areas include:
the cortex cinguli, (next)
parahippocampal gyrus, (next)
cortex insula, (next)
and the orbitofrontal cortex.
Both cortex cinguli and the insula are activated during feeling of disgust, but also, in some cases, during feeling of pleasure, such as aesthetic pleasure. Disgust and pleasure activates, however, different parts of the cingulate cortex and the insula. Remember from Lecture 1 that the insula was activated as response to the golden beauty.
As to the orbitofrontal cortex: In my last lecture we saw that Semir Zeki’s group in London found (2011) that visual art and music that each person find beautiful will result in activation of the medial orbitofrontal cortex. This means that a rock music enthusiast will have his mOFC activated by rock music, and that there may be no response at all in this part of his brain to a work by Mozart. Hence, it depends on the taste of each individual whether the mOFC shall or shall not be activated.
The (next) orbitofrontal cortex is strongly activated in situations when our mind is occupied with thoughts connected with reward, for instance when a beautiful face, or a smile rewards us: For instance, Nakamura et al. (1998) have found a correlated increased activation of the orbitofrontal cortex in a study where male subjects made positive attractiveness judgments of female faces.
The orbitofrontal cortex is perhaps primarily a higher-level sensory cortex for smell and taste, serving as a secondary olfactory and gustatory cortex. This may indicate something significant about the origins of aesthetics in the appraisal of food sources.
An interesting example of activation of the orbitofrontal and insular cortices is their response to the rating of (next) attractiveness and goodness of faces. Faces that we (next) rate as attractive are also rated as good and the more attractive and good the rating is, the more is the activation of the orbitofrontal cortex. The (next) inverse relationship is found for the insular cortex (T. Tzukiura and R. Cabeza, “Shared Brain Activity for Aesthetic and Moral Judgments: Implication for the Beauty-is-Good stereotype”. SCAN (2011) 6, 138-148). (next) (next) (next) (next)
The archicortex
includes the hippocampus, extremely important for our long time memory (next) (next) (next)
and (next) the olfactory cortex, which is the part of cortex receiving impulses from the olfactory apparatus, the olfactory bulbs.
We will (next) now take a closer look on the nerve cells, their anatomy as well as their function. We will start with a presentation of a very significant method to stain neurons, a method that revolutionized our insight into the anatomy of the central nervous system. This is the so called Golgi method after the Italian physician and scientist (next) (next) Camillo Golgi (1843–1926), who discovered it in 1873. It was initially named the black reaction – la reazione nera – but became better known as the Golgi stain or Golgi method.
Golgi’s staining was famously used by the great Spanish neuro-anatomist Santiago Ramón y Cajal (1852–1934) to discover a number of novel facts about the organization of the nervous system, inspiring the birth of the so called “neuron doctrine”.
Golgi’s (next) method stains a limited number of cells at random in their entirety. The mechanism by which this happens is still largely unknown. All parts of the cell are clearly stained in brown and black and can be followed in their entire length, which allowed neuro-anatomists to track connections between neurons and to make visible the complex networking structure of many parts of the brain and spinal cord.
Golgi’s staining is achieved by impregnating fixed nervous tissue with (next) potassium chromate and silver nitrate. Cells thus stained are filled by a micro crystallization of silver chromate, a brown-red crystal. By combining silver nitrate (AgNO3) and potassium chromate (K2CrO4), the silver chromate precipitates inside neurons and makes their morphology visible (next).
The power of the silver chromate staining was initially demonstrated on the (next) Purkinje cells in the cerebellum. I will show you some exemplars of these extremely beautiful cells, stained with the Golgi method, later in my lecture. Interest soon shifted, however, to the retina where (next) Golgi’s student Ferruccio Tartuferi first applied the technique. In his drawing the horizontal and the amacrine cells are clearly represented, as are the rods, cones and bipolar cells, and the ganglion cells. They are seen deep into the relatively thick slice, and, hence, represented with weaker colour strength compared to the other cells. Because of the plexiform microanatomy of the retina, it must have been very evident for Tartuferi that Golgi’s view that the nervous system was an interconnected network, a reticulum, should be retained.
Actually, the significant question raised at this time in history of medicine was whether the nervous system communicates in transverse networks, the view advocated by Golgi and Tartuferi, or, alternatively, it principally is a straightly linear and parallel cell to cell communication, which was the thesis set forth by Santiago Ramon y Cajal?
(next) Finally, H.K. Hartline, R. Granit and G. Wald received the Nobel prize in medicine and physiology in the year 1967 on a basis of studies which gave support to the view of Golgi and Tartuferi; they proved that the nervous system was more of a reticulum that a ”point-to-point” communication.
*
As previously noted, the Purkinje cells of the cerebellum with their beautiful microanatomy inspired much research using Golgi’s method, later improved by Santiago Ramon y Cajal. I will now show you Purkinje cells from rat cerebellum, stained in the silver chromate technique by my own teacher Professor Boleslaw Srebro at the University of Bergen.
next…..next ….next ………..
A nerve cell consists of the so called cell body, or soma, in which the cell nucleus, containing the DNA twisted into chromosomes, is being located. The cell body also contains the synthesis apparatus for proteins, such as enzymes, structural proteins for the cell skeleton and many other sorts of proteins and peptides.
Radiating from this cell body are multiple dendrites, receiving inputs from a vast number of other nerve cells. Leaving the nerve cell body is a single axon, which, in some nerve cells, is very long, leading from the brain to the spinal cord, while it, in other nerve cells may be very, very short. It is the interconnection between different nerve cells within the same area or between different regions of the brain that constitute what we call the neural networks.
From nerve anatomy to physiology
How does one nerve cell communicate with the next? The nerve cells interact with each other through so called synapses, which are of two principal types: electrical synapses and chemical synapses. Here, we will focus on the chemical synapses (slides 113-114), which function through chemical signaling between the presynaptic axon and the postsynaptic dendrite (of the next nerve cell). These synapses have a swollen presynaptic knob, in which there are vesicles filled with neurotransmitter molecules. When the electric impulse reaches this synaptic knob, the vesicles move towards the membrane of the knob, where they empty their content into the synaptic cleft. The neurotransmitter molecules then cross the synaptic cleft by diffusion, and bind to a receptor molecule, following the principle of key in lock: one neurotransmitter fits one receptor. (slide 113)
(slides 115-116) What happens in the postsynaptic nerve when the neurotransmitter binds to the receptor molecule? To answer this question we need to describe how a nerve cell at rest function, a nerve cell that does not send any signal: What I mean is that we need to understand the chemical and electrical properties in these cells.
The chemical concentration of the diverse molecules and ions inside and outside a cell will also determine the electrical properties of the cell. The central question is: what is the difference in electrical potential across the cell membrane? This is utmost important since the nerve cell functions by sending electrical impulses, and, when this happens, there is a transient gross change in the cell membrane potential, (cf. slide 113) running the whole way from the cell body, or soma, to the synaptic knob (domino effect), where, as a consequence, neurotransmitters are released as a response to this signal.
A nerve cell at rest (slide 116) has a high concentration of potassium ions (K+) inside the cell, and a high concentration of sodium ions (Na+) outside the cell. In any chemical system where there is a concentration difference within a solution (put some colour into a glass of water and watch), or between two compartments separated by a permeable membrane, the substances will diffuse from the compartment of high concentration to the compartment of low concentration. In the nerve cell this results in an outflow of K+ ions and an inflow of Na+ ions.
(slide 117) Since the cell membrane is much more permeable to K+ than to Na+, the net flux of K+ out of cell will be much greater than the flux of Na+ into the cell. Since, however, there are multiple huge protein anions inside the cell with a surplus of negative (-) charges on them, molecules which are too large to cross the cell membrane, they will restrict the mobility of the K+ ions:
(slide 118🙂 The K+ ions that leave the cell through the K+ channels will therefore ´hang` on the extracellular face of the cell membrane, being dragged there because of the large negative charges on the inner side of the thin membrane. This establishes an electrical potential between inside and outside equal to -70 millivolt (mV), inside negative, outside positive. This is the so called resting membrane potential.
(slide 119🙂 The diffusion of ions across the cell membrane would have resulted in a dangerous loss of K+, which concentration has to be constant within the cell, and also an accumulation of Na+ inside the cell, if it had not been for the so called Na+/K+ pump. This energy driven pump actively transports three Na+ ions out from the cell in exchange for two K+ ions into the cell to re-establish physiological steady state.
(slides 120-122🙂 Now, if an electrical signal, i.e. a nerve impulse, reaches the nerve end, the synapse, Na + and Ca++ ions will enter the synaptic knob from outside fluid. This will immediately result in a movement of the neurotransmitter-filled vesicles toward the membrane of the synaptic knob. The vesicles fuse with the membrane of the synaptic knob, and empty their content into the synaptic cleft.
Neurotransmitter molecules will now diffuse over the synaptic cleft, and bind to receptor molecules, resulting in influx of Na+ ions into the postsynaptic dendrite: Influx of positive charges will, of course, decrease the potential difference between inside and outside of the dendritic membrane. This potential difference moves down the dendrite (slides 123-124-125) towards the cell body (soma) with some leakage of current out of the cell: let us now say that there is -60mV difference at the so called axon hillock, which is the anatomical site where the axon leaves the cell body.
If this is so, nothing will happen. If, however, the potential between inside and outside is reduced (slides 126-127) to -55mV (the threshold), there will be a change in the membrane properties of the axon[1], leading to a mass influx of Na+, and a total, so called, depolarization of the membrane, changing the membrane potential to +40 mV, now with inside positive, and outside negative. A nerve impulse is then elicited, and when this happens, the impulse will rush down the axon until the synaptic terminal: a domino effect.[2]
The largest nerve cell axons (slide 130), such as those following the sensory and the motoric tracts of in the spinal cord, are encapsulated in neuroglia cells, the so called Schwann cells. As remarked previous in this lecture, the neuroglia are wrapped around the fiber constituting a so called myelin sheath, a fat layer, insulating the fiber; that is, it cannot lead electrical current.
Since, however, the Schwann cells are separated by small patches of free cell membrane, the so called nodes of Ranvier, the nerve impulse will be speeded up: What happens is that the nerve impulse jumps[3] from one node of Ranvier to the next, which speeds up the impulse substantially. This is absolute essential for the rapid responses of our muscles, say in a situation where we have to run away from a danger threatening us.
[1] In the axon membrane there are voltage sensitive channels for sodium, and these will remain close if the membrane potential is more polarized then -55 mV. At -55mV the channel is so unstable that it will allow some influx of Na+. This will lead to further opening of the channel, and, hence, a mass influx of Na+.
[2] The axon is repolarized through a process where the Na+ channels closes. K+ will then flux out of cell, transiently hyperpolarizing the cell. The Na+/K+ pump restabilizes the membrane at -65 mV.
[3] The Na+ ions which enter the axon will “jump” to the next node of Ranvier, depolarizing its membrane, which will lead to an opening of the voltage sensitive Na+ channels in this node, leading to a new mass influx of Na+ ions, and so on, until the synaptic terminal.