Color Atlas of Physiology 2003 thieme

F. Tracts and function of cerebellum

Plate 12.10 Motor System III

ity because the extensor effect of Deiter’s nucleus predominates.

The integrating and coordinating function of the sensorimotor system can be illustrated in two tennis players. When one player serves, the body of the other player moves to meet the ball (goal-directed movement) while using the right leg for support and the left arm for balance (postural motor control). The player keeps his eye on the ball (oculomotor control) and the visual area of the cortex assesses the trajectory and velocity of the ball. The associative cere-

used to perceive and assess signals from the “outer world” and from memories. Processing of both types of input is important for behavior.

Programmed behavior (!A). The lateral hypothalamus has various programs to control lower hormonal, autonomic and motor processes. This is reflected internally by numerous autonomic and hormonal activities, and is reflected outwardly by different types of behavior.

Different programs exist for different behavioral reactions, for example:

Defensive behavior (“fight or flight”). This program has somatic (repulsive facial expression and posture, flight or fight behavior), hormonal (epinephrine, cortisol) and autonomic (sympathetic nervous system) components. Its activation results in the release of energy-rich free fatty acids, the inhibition of insulin release, and a decrease in blood flow to the gastrointestinal tract as well as to rises in cardiac output, respiratory rate, and blood flow to the skeletal muscles.

Physical exercise. The components of this program are similar to those of defensive behavior.

Nutritive behavior, the purpose of which is to ensure an adequate supply, digestion and intake of foods and liquids. This includes searching for food, e.g. in the refrigerator, activation of the parasympathetic system with increased gastrointestinal secretion and motility in response to food intake, postprandial reduction of skeletal muscle activity and similar activities.

Reproductive behavior, e.g., courting a partner, neuronal mechanisms of sexual response, hormonal regulation of pregnancy (!p. 304), etc.

Thermoregulatory behavior, which enables us to maintain a relatively constant core temperature (!p. 224), even in extreme ambient temperatures or at the high level of heat production during strenuous physical work.

Monoaminergic neuron systems contain neurons that release the monoamine neurotransmitters norepinephrine, epinephrine, dopamine, and serotonin. These neuron tracts extend from the brain stem to almost all parts of the brain and play an important role in the overall regulation of behavior. Experimental activation of noradrenergic neurons, for example, led to positive reinforcement (liking, rewards), whereas the serotoninergic neurons are thought to be associated with dislike. A number of psychotropic drugs target monoaminergic neuron systems.

areas of the ipsilateral cortex (association fibers) or to areas of the contralateral cortex (commissural fibers) (!A2); only a few extend to the periphery (!A4 and p. 325 C). Locally, the pyramidal cells are connected to each other by axon collaterals. The principal dendrite of a pyramidal cell projects to the upper layers of its column and has many thorn-like processes (spines) where many thalamocortical, commissural and association fibers terminate. The afferent fibers utilize various transmitters, e.g., norepinephrine, dopamine, serotonin, acetylcholine and histamine. Inside the cerebral cortex, information is processed by many morphologically variable stellate cells (!A1), some of which have stimulatory effects (VIP, CCK and other peptide transmitters), while others have inhibitory effects (GABA). Dendrites of pyramidal and stellate cells project to neighboring columns, so the columns are connected by thousands of threads. Plasticity of pyramidal cell synapses — i.e., the fact that they can be modified in conformity with their activity pattern — is important for the learning process (!p. 336).

Cortical potentials. Similar to electrocardiography, collective fluctuations of electrical potentials (brain waves) in the cerebral cortex can be recorded by electroencephalography using electrodes applied to the skin over the cranium (!B). The EPSPs contribute the most to the electroencephalogram (EEG) whereas

332the share of the relatively low IPSPs (!p. 50ff.) generated at the synapses of pyramidal cell

dendrites is small. Only a portion of the rhythms recorded in the EEG are produced directly in the cortex (α and γ waves in conscious perception; see below). Lower frequency waves from other parts of the brain, e.g. α waves from the thalamus and θ waves from the hippocampus, are “forced on” the cortex (brain wave entrainment).

By convention, downward deflections of the EEG are positive. Generally speaking, depolarization (excitation) of deeper layers of the cortex and hyperpolarization of superficial layers cause downward deflection (+) and vice versa.

Brain wave types. The electrical activity level of the cortex is mainly determined by the degree of wakefulness and can be distinguished based on the amplitude (a) and frequency (f) of the waves (!B, C). α Waves (f !10 Hz; a !50 µV), which predominate when an adult subject is awake and relaxed (with eyes closed), are generally detected in multiple electrodes (synchronized activity). When the eyes are opened, other sensory organs are stimulated, or the subject solves a math problem, the α waves subside (α blockade) and " waves appear (f !20 Hz). The amplitude of # waves is lower than that of α waves, and they are chiefly found in occipital (!B) and parietal regions when they eyes are opened. The frequency and amplitude of # waves varies greatly in the different leads (desynchronization). # Waves reflect the increased attention and activity (arousal activity) of the ascending reticular activating system

(ARAS; !p. 322). γ Waves (!30 Hz) appear during learning activity. Low-frequency θ waves appear when drowsiness descends to sleep (sleep stages A/B/C; !D); they transform into even slower δ waves during deep sleep (!C, D).

The EEG is used to diagnose epilepsy (localized or generalized paroxysmal waves and spikes; !C), to assess the degree of brain maturation, monitor anesthesia, and to determine brain death (isoelectric EEG).

Magnetoencephalography (MEG), i.e. recording magnetic signals induced by cortical ion currents, can be combined with the EEG to precisely locate the site of cortical activity (resolution a few mm).

A. Cortical layers I–VI (multiple view of a single-cortex column)

V

VI

Surface

B. Recording the electroencephalogram (EEG)

12 Central Nervous System and Senses

334

12 Central Nervous System and Senses

336

Consciousness, Memory, Language

Consciousness. Selective attention, abstract thinking, the ability to verbalize experiences, the capacity to plan activities based on experience, self-awareness and the concept of values are some of the many characteristics of consciousness. Consciousness enables us to deal with difficult environmental conditions (adaptation). Little is known about the brain activity associated with consciousness and controlled attention (LCCS, see below), but we do know that subcortical activation systems such as the reticular formation (!p. 322) and corticostriatal systems that inhibit the afferent signals to the cortex in the thalamus (!p. 326) play an important role.

Attention. Sensory stimuli arriving in the sensory memory are evaluated and compared to the contents of the long-term memory within fractions of a second (!A). In routine situations such as driving in traffic, these stimuli are unconsciously processed (automated attention) and do not interfere with other reaction sequences such as conversation with a passenger. Our conscious, selective (controlled) attention is stimulated by novel or ambiguous stimuli, the reaction to which (e.g., the setting of priorities) is controlled by vast parts of the brain called the limited capacity control system (LCCS). Since our capacity for selective attention is limited, it normally is utilized only in stress situations.

The implicit memory (procedural memory) stores skill-related information and information necessary for associative learning (conditioning of conditional reflexes; !p. 236) and non-associative learning (habituation and sensitization of reflex pathways). This type of unconscious memory involves the basal ganglia, cerebellum, motor cortex, amygdaloid body (emotional reactions) and other structures of the brain.

The explicit memory (declarative/knowledge memory) stores facts (semantic knowledge) and experiences (episodic knowledge, especially when experienced by selective attention) and consciously renders the data. Storage of information processed in the uniand polymodal association fields is the responsibility of the temporal lobe system (hip-

pocampus, perirhinal, entorhinal and parahippocampal cortex, etc.). It establishes the temporal and spatial context surrounding an experience and recurrently stores the information back into the spines of cortical dendrites in the association areas (!p. 322). The recurrence of a portion of the experience then suffices to recall the contents of the memory.

Explicit learning (!A) starts in the sensory memory, which holds the sensory impression automatically for less than 1 s. A small fraction of the information reaches the primary memory (short-term memory), which can retain about 7 units of information (e.g., groups of numbers) for a few seconds. In most cases, the information is also verbalized. Long-term storage of information in the secondary memory (long-term memory) is achieved by repetition (consolidation). The tertiary memory is the place where frequently repeated impressions are stored (e.g., reading, writing, one’s own name); these things are never forgotten, and can be quickly recalled throughout one’s lifetime. Impulses circulating in neuronal tracts are presumed to be the physiological correlative for short-term (primary) memory, whereas biochemical mechanisms are mainly responsible for long-term memory. Learning leads to long-term genomic changes. In addition, frequently repeated stimulation can lead to long-term potentiation (LTP) of synaptic connections that lasts for several hours to several days. The spines of dendrites in the cortex play an important role in LTP.

Mechanisms for LTP. Once receptors for AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) are activated by the presynaptic release of glutamate (!p. 55 F), influxing Na+ depolarizes the postsynaptic membrane. Receptors for NMDA (N- methyl-D-aspartic acid) are also activated, but the Ca2+ channels of the NMDA receptors are blocked by Mg2+, thereby inhibiting the influx of Ca2+ until the Mg2+ block is relieved by depolarization. The cytosolic Ca2+ concentration [Ca2+]i then rises. If this is repeated often enough, calmodulin mediates the autophosphorylation of CaM kinase II (!p. 36), which persists even after the [Ca2+]i falls back to normal. CaM kinase II phosphorylates AMPA receptors (increases their conductivity) and promotes their insertion into the postsynaptic membrane, thereby enhancing synaptic transmission over longer periods of time (LTP).

Plate 12.14 Consciousness, Memory, Language

Amnesia (memory loss). Retrograde amnesia

(loss of memories of past events) is characterized by the loss of primary memory and (temporary) difficulty in recalling information from the secondary memory due to various causes (concussion, electroshock, etc.). Anterograde amnesia (inability to form new memories) is characterized by the inability to transfer new information from the primary memory to the secondary memory (Korsakoff’s syndrome).

Language is a mode of communication used

(1) to receive information through visual and aural channels (and through tactile channels in the blind) and (2) to transmit information in written and spoken form (see also p. 370). Language is also needed to form and verbalize concepts and strategies based on consciously processed sensory input. Memories can therefore be stored efficiently. The centers for formation and processing of concepts and language are unevenly distributed in the cerebral hemispheres. The left hemisphere is usually

the main center of speech in right-handed individuals (“dominant” hemisphere, large planum temporale), whereas the right hemisphere is dominant in 30–40% of all left-hand- ers. The non-dominant hemisphere is important for word recognition, sentence melody, and numerous nonverbal capacities (e.g., music, spatial thinking, face recognition).

This can be illustrated using the example of patients in whom the two hemispheres are surgically disconnected due to conditions such as otherwise untreatable, severe epilepsy. If such a split-brain patient touches an object with the right hand (reported to the left hemisphere), he can name the object. If, however, he touches the object with the left hand (right hemisphere), he cannot name the object but can point to a picture of it. Since complete separation of the two hemispheres also causes many other severe disturbances, this type of surgery is used only in patients with otherwise unmanageable, extremely severe seizures.

337

12 Central Nervous System and Senses

338

Glia

The central nervous system contains around 1011 nerve cells and 10 times as many glia cells such as oligodendrocytes, astrocytes, ependymal cells, and microglia (!A). Oligodendrocytes (ODC) form the myelin sheath that surrounds axons of the CNS (!A).

Astrocytes (AC) are responsible for extracellular K+ and H+ homeostasis in the CNS. Neurons release K+ in response to high-frequency stimulation (!B). Astrocytes prevent an increase in the interstitial K+ concentration and thus an undesirable depolarization of neurons (see Nernst equation, Eq. 1.18, p. 32) by taking up K+, and intervene in a similar manner with H+ ions. Since AC are connected by gap junctions (!p. 16ff.), they can transfer their K+ or H+ load to nearby AC (!B). In addition to forming a barrier that prevents transmitters from one synapse from being absorbed by another, AC also take transmitters up, e.g. glutamate (Glu). Intracellular Glu is converted to glutamine (GluNH2), then transported out of the cell and taken up by the nerve cells, which convert it back to Glu (transmitter recycling; !B).

Some AC have receptors for transmitters such as Glu, which triggers a Ca2+ wave from one AC to another. Astrocytes are also able to modify the Ca2+ concentration in the neuronal cytosol so that the two cell types can “communicate” with each other. AC also mediate the transport of materials between capillaries and neurons and play an important part in energy homeostasis of the neurons by mediating glycogen synthesis and breakdown.

During embryonal development, the long processes of AC serve as guiding structures that help undifferentiated nerve cells migrate to their target areas. Glia cells also play an important role in CNS development by helping to control gene expression in nerve cell clusters with or without the aid of growth factors such as NGF (nerve growth factor), BDGF (brain-derived growth factor), and GDNF (glial cell line-derived neurotropic factor). GDNF also serves as a trophic factor for all mature neurons. Cell division of glia cells can lead to in scarring (epileptic foci) and tumor formation (glioma).

Immunocompetent microglia (!A) assume many functions of macrophages outside the CNS when CNS injuries or infections occur (!p. 94ff.). Ependymal cells line internal hollow cavities of the CNS (!A).

Sense of Taste

Gustatory pathways. The taste buds (!D) consist of clusters of 50–100 secondary sensory cells on the tongue (renewed in 2-week cycles); humans have around 5000 taste buds. Sensory stimuli from the taste buds are conducted to endings of the VIIth, IXth and Xth cranial nerves, relayed by the nucleus tractus solitarii, and converge at a high frequency on

(a) the postcentral gyrus via the thalamus (!p. 323 B, “tongue”) and (b) the hypothalamus and limbic system via the pons (!C).

The qualities of taste distinguishable in humans are conventionally defined as sweet, sour, salty, and bitter. The specific taste sensor cells for these qualities are distributed over the whole tongue but differ with respect to their densities. Umami, the sensation caused by monosodium-L-glutamate (MSG), is now classified as a fifth quality of taste. MSG is chiefly found in protein-rich foods.

Taste sensor cells distinguish the types of taste as follows: Salty: Cations (Na+, K+, etc.) taste salty, but the presence of anions also plays a role. E.g., Na+ enters the taste sensor cell via Na+ channels and depolarizes the cell. Sour: H+ ions lead to a more frequent closure of K+ channels, which also has a depolarizing effect. Bitter: A family of !50 genes codes for an battery of bitter sensors. A number of sensory proteins specific for a particular substance are expressed in a single taste sensor cell, making it sensitive to different bitter tastes. The sensory input is relayed by the G-protein α-gustducin. No nuances but only the overall warning signal “bitter” is perceived. Umami: Certain taste sensor contain a metabotropic glutamate receptor, mGluR4, the stimulation of which leads to a drop in cAMP conc.

Taste thresholds. The threshold (mol/L) for recognition of taste stimuli applied to the tongue is roughly 10– 5 for quinine sulfate and saccharin, 10– 3 for HCl, and 10– 2 for sucrose and NaCl. The relative intensity differential threshold I/I (!p. 352) is about 0.20. The concentration of the gustatory stimulus determines whether its taste will be perceived as pleasant or unpleasant (!E). For the adaptation of the sense of taste, see p. 341 C.

Function of taste. The sense of taste has a protective function as spoiled or bitter-tasting food (low taste threshold) is often poisonous. Tasting substances also stimulate the secretion of saliva and gastric juices (!pp. 236, 242).