Cerebellum Neuroanatomy 2024 PDF

The Cerebellum IZN Heidelberg Neuroanatomy Course Gonzalo Alvarez-Bolado 2024 Intro: Walking like a drunkard 1. What is the cerebellum? 2. Macroscopic appearance 3. Function of the cerebellum 4. Connections 5. Circuits in the cerebellar cortex 6. How does it work? ...

The Cerebellum IZN Heidelberg Neuroanatomy Course Gonzalo Alvarez-Bolado 2024 Intro: Walking like a drunkard 1. What is the cerebellum? 2. Macroscopic appearance 3. Function of the cerebellum 4. Connections 5. Circuits in the cerebellar cortex 6. How does it work?  Walking like a drunkard-1 (Clinical case from Blumenfeld 2nd Ed. 2010) A 76-year-old man with a history of cigarette smoking developed progressive difficulty walking over the course of 1 month. He noticed that when he stood up he felt “woozy,” and he described his gait as feeling like he was drunk, saying “my legs go one way, and I go the other.” His family said he frequently lost his balance, with staggering and unsteadiness. He also had frequent mild headaches that occurred at any time of the day and night and seemed to be getting worse. Exam was unremarkable except for a wide-based, unsteady gait, tending to fall to the left, especially with tandem walking. Of note, there was no ataxia on finger-to-nose or heel- to- shin testing, and rapid alternating movements were normal. There was no history of alcohol intake.  Walking like a drunkard-2 (Clinical case from Blumenfeld 2nd Ed. 2010) 1. On the basis of those symptoms and signs, where is the lesion? 2. What is the most likely diagnosis, and what are some other possibilities? The patient had truncal ataxia,with no significant appendicular ataxia.This symptom may be caused by a lesion of the cerebellar vermis. Other possibilities of this gait disorder include hydrocephalus or a lesion of the frontal lobes or spinal cord, although additional abnormalities on exam are often (but not always) present with these disorders. The presence of headache suggests that the lesion is intracranial. The most likely clinical localization is cerebellar vermis. Given the history of cigarette smoking and the gradual onset of symptoms, metastatic lung cancer to the cerebellar vermis should be seriously considered. Walking like a drunkard-3 (Clinical case from Blumenfeld 2nd Ed. 2010) 1. What is the cerebellum? The cerebellum is an organ of the CNS dedicated to motor coordination. It sits like a backpack on the “back” (dorsal side) of the brainstem supported by three thick bilateral axonal bundles (the cerebellar peduncles), which carry its inputs and outputs. The inputs to the cerebellum come from peripheral receptors as well as spinal cord, cortex and tectum. The outputs go to: 1) thalamus (and from there to the motor cortex) 2) brainstem centers (red nucleus, vestibular nuclei, reticular nuclei) and from there to the spinal cord. 2. Macroscopic appearance In mammals, the cerebellum consists of two large lateral hemispheres united by a midline vermis. The cerebellar surface is divided by numerous curved transverse fissures which separate its folia and give it a laminated appearance. The deepest fissures divide it into lobes and lobules. Deep Cerebellar Nuclei 3. Function of the cerebellum-1 During motor learning the cerebellum stores info that later will allow for precise: Coordination of movements Synergy (cooperation) between muscles Timing of movements Targeting of movements Strength (appropriate for a certain movement) Muscle tone 3. Function of the cerebellum-2 Unconscious Computer-like feedback loops Moment-to-moment adjustments to changing conditions Moment-to-moment adjustments to maintain balance Ipsilateral control (right side of cerebellum coordinates right side movements)  3. Function of the cerebellum-3 ANAMNESIS: A 24-year-old female patient was admitted to hospital complaining of dizziness and the inability to walk steadily for more than 20 years, and nausea and vomiting for 1 month. She is married and has a daughter. Family entirely normal. She was 4 years old before she could stand unassisted, and did not begin to walk unassisted until the age of 7, with a persistently unsteady gait. She never ran or jumped. Her speech was not intelligible until 6 years of age and she did not enter school.  3. Function of the cerebellum-4 CLINICAL EXAMINATION: The patient could cooperate and fully orientate. Her word comprehension and expression remained intact, no sign of aphasia, but mild to moderate signs of cerebellar dysarthria. The patient has mild voice tremor with slurred pronunciation and her voice quality is slightly harsh. Cerebellar ataxia including Romberg’s sign, and there is evidence of heel-knee-tibia impairment. The patient experienced mild to moderate dysmetria in reaching the nose when adminis- tered the finger-to-nose test. Pronation-supination alternating (dis-diadocokinesia) movements were slightly irregular and slowed. She is able to walk unsteadily without support, her gait is moderately unsteady. The patient has evidence of tandem gait and moderately reduced gait speed. 3. Function of the cerebellum-5  e t t er 4. Connections i t b ay do is w th Pedunculus superior: mostly efferents (to Motor Cortex Motor Thalamus Reticular formation, Red do it better nucleus, Motor Thalamus) this way this is what I am doing Pedunculus inferior: Pedunculus medius: efferents and afferents. only afferents Afferents from the Inferior Olive, Spinal (collaterals of the Cord, Vestibular Nuclei und Trigeminus. ys th s pa atu wa cortico-spinal axons; Efferents to the Inferior Olive or st status of relay in the pontine ot y m odif spinal motor nuclei) m pathways in bl ice is of go sta n th lik e, ep nd am e ke a w I skin receptors g no muscle receptors joint receptors ! ! ng ce hi n et la m ba so f Spinal Cord o to D ou m Ia Vestibular Nuclei (balance) 5. Cells and Circuits-1 5. Cells and circuits-2 y e r u la r la e c mol l a y er e c ell nj Purki y er le l a r a n u g  5. Cells and circuits-3 Stellate Cell Molecular Layer Purkinje Cell Parallel Fiber Basket Cell Cerebellar Glomerulus Purkinje Cell Purkinje Layer Cell Golgi Cell Granule Cell Climbing Fiber Granule Cell Layer Mossy Fiber White Cerebellar Nuclei Matter  5. Cells and circuits-4 Granule cells Purkinje cells inhibitory interneurons Afferents Collaterals Cerebellar Collaterals nuclei Climbing Efferents Mossy fibers fibers Thalamus Pontine nuclei, Inferior Olive Red nucleus, Spinal cord, Vestibular nuclei, Vestibular nuclei Reticular formation 6. How does it work?-1 6. How does it work?-2 6. How does it work?-3 6. How does it work?-4 P. R. Bandyopadhyay „We assume that the principles of integrated design are derived from the olivo-cerebellar motion control laws, as evidenced by the dynamics of the inferior olive neurons that are responsible for motion and balance in all mammals, from rats to human beings. The motion control laws are self-regulating: a conventional closed control loop is not present. This makes them very robust. For this reason, this type of controllers has remained unchanged in many animals.“ End  The Diencephalon IZN Heidelberg Neuroanatomy Course Gonzalo Alvarez-Bolado 2023  1. What is the diencephalon? 5 4 3 2 1 0 -1 -2 -3 -4 -5 -6 -7 -8 Bregma Lambda Bregma Hippocampus Inferior Colliculus Cerebellum Cerebral Cortex Superior Colliculus corpus callosum Hippoc Olfactory Bulb LV posterior com Septum Midbrain 4V Thalamus anterior fornix commissure Pons Medulla Preoptic Area Hypothalamus Spinal Interaural Cord Lateral 0.24 mm Interaural 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4 Diencephalon = Thalamus Click on sagittal diagram + Hypothalamus to go the corresponding coronal diagram 1. What is the diencephalon?  1. What is the diencephalon? M1 M2 RSA S1HL S1DZ S1ShNc RSG cg S1BF Or IG cc Py df CA3 LV dhc GrDG ec Mol DG D3V LDVL fi AD MHb sm S2 LDDM BSTS st LHb AV MD PV Rt PC VL IAD ic GI CPu CM VPL AM DI IAM VA rf Sub Rh mt AIP Cl LGP IPAC VM B Re La AStr DEn Xi B ZI CeC PaMP PaDC SLEAC CeMAD PaLM Pir BLA PaMM f LH mfb CeMAV MeAD VEn AHP IM SO Cir BMA MeAV SPa 3V opt Pe CxA RCh ACo sox BAOT Interaural 2.86 mm Bregma -0.94 mm  1. What is the diencephalon? M1 M2 RSA S1HL S1DZ S1ShNc RSG cg S1BF Or IG cc Py df CA3 LV dhc GrDG ec Mol DG D3V LDVL fi AD MHb sm S2 LDDM BSTS st LHb AV MD PV Rt PC VL IAD ic GI CPu CM VPL AM DI IAM VA rf Sub Rh mt AIP Cl LGP IPAC VM B Re La AStr DEn Xi B ZI CeC PaMP PaDC SLEAC CeMAD PaLM Pir BLA PaMM f LH mfb CeMAV MeAD VEn AHP IM SO Cir BMA MeAV SPa 3V opt Pe CxA RCh ACo sox BAOT Interaural 2.86 mm Bregma -0.94 mm The Thalamus  2. What is the thalamus? Epithalamus or Habenula S1HL M1 M2 RSA Dorsal thalamus S1DZ S1ShNc (or simply “Thalamus”) RSG cg S1BF Or IG cc Py df CA3 LV dhc GrDG ec Mol DG D3V LDVL fi AD MHb sm S2 LDDM BSTS st LHb AV MD PV Rt PC VL IAD ic GI CPu CM VPL AM DI IAM VA rf Sub Rh mt AIP Cl LGP IPAC VM B Re La AStr DEn Xi B ZI CeC PaMP PaDC SLEAC CeMAD PaLM Pir BLA PaMM f LH mfb CeMAV MeAD VEn AHP IM SO Cir BMA MeAV SPa 3V opt Pe CxA RCh ACo sox BAOT Interaural 2.86 mm Bregma -0.94 mm Ventral thalamus (or simply “Nucleus reticularis”)  2. What is the thalamus? S1HL M1 M2 RSA Dorsal thalamus S1DZ S1ShNc RSG cg S1BF Or IG cc Py df The dorsal thalamus CA3 LV dhc GrDG ec Mol DG D3V S2 BSTS LDDM LDVL AD MHb LHb sm fi st (or simply “the thalamus”) PV is an obligatory relay AV MD Rt PC VL IAD ic GI CPu CM VPL AM DI AIP Cl LGP VA Sub IAM Rh mt rf (Zwischenstation) VM for sensory inputs going to the IPAC B Re La AStr DEn Xi B ZI CeC PaMP PaDC SLEAC CeMAD PaLM Pir VEn BLA IM CeMAV MeAD SO LH PaMM AHP Cir f mfb cortex BMA MeAV SPa 3V opt Pe CxA RCh ACo sox BAOT Interaural 2.86 mm Bregma -0.94 mm 2. What is the thalamus? The thalamus (also called “the dorsal thalamus”) is an obligatory relay (Zwischenstation) for sensory inputs going to the cortex  3. Organization of the thalamus The thalamus is an ovoid mass of neuronal nuclei (120 in humans) subdivided by a Y- shaped wall of axons, the “lamina medullaris”. Anterior Those nuclei projecting to the cortex are called M “specific”, and those projecting to other ed thalamic nuclei, to the brainstem, diencephalon ia l or striatum are called “non-specific”. Ventro- Lateral The specific nuclei form four groups: Dorsal two of them are famous and well-known: VENTRO-LATERAL: somatosensory, motor DORSAL: visual, auditory, pulvinar the other two are somewhat mysterious: Left-side Human Thalamus ANTERIOR: limbic (=emotional) MEDIAL: (self-awareness-related?) 4.1. VENTRO-LATERAL: Somatosensory thalamus Some ventro-lateral nuclei receive all the somatosensory afferents from the skin of the entire body as well as the conscious information from the muscles and joints. Somatosensory means: - touch (tactile information) plus - conscious proprioceptive (conscious information about the state of muscles and joints). They relay this information to the primary somatosensory areas of the cortex. Since the thalamus can selectively filter access of somatosensory inputs to the cortex, it has been called “The Gate to Consciousness”. A very small area of the VPM nucleus receives the gustatory information (sense of taste). It projects to the anterior insular cortex and the frontal operculum.  4.2. VENTRO-LATERAL: Motor thalamus premotor motor cortex cortex We have seen that some ventro-lateral nuclei receive all the somatosensory afferents… …other ventro-lateral nuclei receive afferents from the globus pallidus (basal ganglia: motor control) and from the cerebellum (motor control). They relay this information to the primary and secondary motor areas of the cortex. This part of the thalamus is integrated in the motor control loop together with the cerebellum and basal ganglia.  5.1. DORSAL: Visual and Auditory thalamus au rtex dit co ory u al vis tex r co The corpus geniculatum laterale is the relay for the visual pathway. Receives axons from the retina and projects to the primary visual cortex. The corpus geniculatum mediale is the relay for the auditory pathway. 5.2. DORSAL: The Pulvinar The pulvinar (“polster” or “pillow”) receives afferents from the thalamus and projects to association areas of the occipital and parietal cortex. Very important for the visual attention system. It exists only in primates. Pulvinar 6. ANTERIOR: The limbic thalamus The anterior group receives afferents from the mammillary body, a large hypothalamic nucleus, and sends efferents to the cingular cortex. The cingular cortex projects to the hippocampus, and the hippocampus sends most of its axons to the mammillary body. This is the “Papez circuit”, very important for the limbic system (the emotional brain). 7. MEDIAL: Self-awareness circuits…? The medial thalamic nuclei project to the frontal lobe of the cortex. If any part of this circuit is lesioned, patients show a syndrome called “moria” (pathological giddiness or inappropriate laughter; German: Witzelsucht). It is believed that this circuit regulates some of the most important aspects of personality and character. The medial thalamic nuclei receive afferences from thalamus, hypothalamus, mesencephalon and pallidum. What happens with the sense of smell? Medio-dorsal thalamic nucleus…? The Hypothalamus 1. What is the hypothalamus? The hypothalamus is a complex, loosely organized region with three important functions: the homeostasis or maintenance of the internal milieu (temperature, energie, pH, Oxygen, Osmolarity...) the survival of the individual Agression, Fight-or-Flight, self-protection… the survival of the species reproduction, parental behavior... 18 1. What is the hypothalamus? To carry out these functions the hypothalamus controls several instruments: Endocrine system secretion of hormones Autonomous nervous system Sympathetic, Parasympathetic Circadian Rythms sleep-wake cycle Motivated behavior stereotyped behaviors moved by instinct or internal drive (eating behavior, drinking behavior...) 19  1. What is the hypothalamus? Regions PREOPTIC SUPRAOPTIC ANTERIOR TUBERAL MAMMILLARY LATERAL LPO LH LH LH MCPO SO SUM DMH Zones MIDDLE MPO AH VMH MBO SCh PVH PERI- ARC VENTRICULAR The hypothalamus is formed AD PV by a large number of nuclei embedded in a reticular (= not organized into nuclei) mass of neurons. Hypothalamic nuclei can be roughly subdivided into three zones and four regions 20  2. What is homeostasis? The most important function of the hypothalamus is the homeostasis, or “maintenance of the internal milieu” Information Reaction “set point” Neural afferences Autonomous System Humoral afferences Endocrine System Motivated behavior Sleep-Wake cycle Temperature 21  3. HUMORAL afferences and efferences of the Hypothalamus The hypothalamus receives axonal afferences and sends axonal efferences like any other brain region. Particularly important are those linking the hypothalamus to the autonomous (vegetative) nervous system. Specific to the hypothalamus however are the HUMORAL afferences and efferences. HUMORAL refers to information carried by the blood and not by AXONS. Humoral hypothalamic afferences - Glucose level and Leptin (and other molecules) inform about the energy balance - Osmolarity informs about the water balance - Temperature - Hormon level informs about the endocrine system (feedback loop) Humoral hypothalamic efferences Secretion of hypothalamic hormones through: - Neurohypophysis (magnocellular System) >>> to the general bloodstream - parvocellular System >>> to the Adenohypophysis - Adenohypophysis >>> to the general bloodstream 22  4. The circumventricular organs (CVOs) How can HUMORAL afferences (carried by the blood) reach the hypothalamic neurons, since these reside in the brain and are protected by the blood-brain-barrier? HUMORAL afferences reach hypothalamic neurons by using Circumventricular Organs (CVOs) CVOs are unpaired, medial, specialized areas of the wall of the ventricular system of the brain: Organum subfornicale Organum vasculosum laminae terminalis Eminentia mediana Organum subcommissurale (the Glandula pinealis and Area postrema are also CVOs but less important in this context) These organs have many capillaries with pores and do not have a blood-brain-barrier (BBB) (they are also called neurohemal regions). Since they do not have BBB, in the CVOs neurons contact directly the substances of the blood. In this way they can measure different parameters like osmolarity, hormones, fever-inducing substances or pyrogens (Interleukin-1, bacterial pyrogens). 23  5. The hungry hypothalamus: Arcuate nucleus and eating behavior Perhaps the most well-known and well-researched function of the hypothalamus is the control of eating behavior. 488 H.-R. Berthoud / Physiology & Behavior 91 (2007) 486–498 Fig. 2. Neural network controlling food intake and energy balance. Schematic diagram of information flow involved in both internal-homeostatic and external control of food intake and energy balance. Signaling from the internal milieu or external environment to the brain is either mediated by primary and higher order sensory Because of obesity, which has become a serious health problem all over the world, the neurons or hormones and substrates. Centrifugal signaling from the brain to the effector organs is either mediated by premotor and motor neurons or by hormones. hypothalamus is today the object of much research. Eating behavior is a motivated behavior, i.e. a Abbreviations: ACB, nucleus accumbens; AIC, agranular insular cortex; AMY, amygdala; AP, area postrema; ARC, arcuate nucleus; dmnX, dorsal motor nucleus of vagus; LH, lateral hypothalamus; HIP, hippocampus; MoN, motor nuclei for oro-motor control; NTS, nucleus tractus solitarius; OLF, olfactory bulb; PFC, prefrontal behavior with a clear objective, stereotyped and driven by instinct. The hypothalamus is a very cortex; PIR, piriform cortex; PIT, pituitary gland; PRL, prelimbic cortex; PVN, paraventricular nucleus of the hypothalamus; RF, medullary reticular formation; important part of the complex system that regulates eating behavior. 24 RVLM, rostroventrolateral medulla; SNS, sympathetic nervous system; V1/V4, visual processing areas 1,4; V, facial nerve; VII, trigeminal nerve; IX, glosso- pharyngeal nerve.  5. The hungry hypothalamus: Arcuate nucleus and eating behavior The arcuate nucleus is a key regulator of the eating behavior. It contains two kinds of neurons: 1) some express NPY and AGRP; their activation promotes eating; 2) some express POCM and CART; their activation promotes satiety (not-eating). The neurons of the arcuate can detect our energy level, because they are sensitive to glucose, fatty acids, amino acids, insulin, grehlin, PYY and leptin 25 End  The Basal Ganglia IZN Heidelberg Neuroanatomy Course Gonzalo Alvarez-Bolado 2024  1 WHAT ARE THE BASAL GANGLIA?  1. What are the basal ganglia? * The telencephalon (or “endbrain”) is formed by the olfactory bulb, the cerebral cortex, formed by layers of neurons, and the cerebral nuclei (a.k.a. basal nuclei or BASAL GANGLIA), which are gray substance aggregates, i.e. neuronal nuclei. GENSAT Project, Rockefeller University, Mouse Brain Atlas, gensat.org A very important function of the BASAL GANGLIA is MOTOR CONTROL. PLANNING: Intentional movements start with planning in the association cortex. PROGRAMMING: Cerebellum and basal ganglia program in parallel the motion sequence and inform the premotor cortex about these plans. EXECUTION: the premotor cortex passes this information to the motor cortex, which sends the appropriate instructions to the spinal alpha- motoneurons through the pyramidal pathway. CONTROL: control feedbacks from the CP and GP and cerebellum. CONTROL: sensory control feedbacks from the somatosensory pathways.  2 BASAL GANGLIA NOMENCLATURE 2. Nomenclature of the Basal Ganglia Here we see the entire CNS represented as a “flat map” according to Larry Swanson (USC). According to their functions and connections, the basal ganglia, also called “cerebral nuclei”, form two groups: the striatum and the pallidum. The dorsal striatum is called caudoputamen (CP) and the dorsal pallidum is called globus pallidus (GP). Caudoputamen (CP) and globus pallidus (GP) are the best understood parts of the basal ganglia. However, there are also ventral, medial and Larry W. Swanson (2012) “Brain Architecture: Understanding the Basic Plan” caudorostral striatum and Oxford University Press pallidum  2. Nomenclature of the Basal Ganglia The dorsal striatum is called caudoputamen (CP) The basal ganglia can simply be divided into Striatum and Pallidum. Larry W. Swanson (2012) “Brain Architecture: and the dorsal pallidum is called globus pallidus (GP). Understanding the Basic Plan” Caudoputamen (CP) Oxford University Press and globus pallidus (GP) are the best understood parts of the basal ganglia. Basal Ganglia There are also a ventral, medial and caudorostral striatum, and a ventral, dorsal and caudorostral pallidum. These subdivisions include the septum, the accumbens, the amygdala and part of the preoptic area… but all that is beyond the scope of this introduction.  2. Nomenclature of the Basal Ganglia Striatum Septum (Caudate-Putamen S1HL M1 M2 or S1DZ S1FL Cg1 Caudoputamen) Cg2 cg S1BF IG cc LSD LV ec df TS SFi S2 CPu SFO vhc Pallidum GI BSTS D3V st ic (Globus pallidus) BSTMPM sm DI PVA LGP rf BSTMPI f AIP ADP Cl A14 IPACL 3V IPACM AC BSTLP DEn Pe acp VP Amygdala BSTMPL SLEA I Pir I SI VEn MPOM LPO MPOL mfb AAD MCPO CxA HDB MPA ACo AAV ox LOT SCh Paxinos, Franklin “The mouse brain in stereotaxic coordinates” (2001) Academic Press mouse brain  2. Nomenclature of the Basal Ganglia Septum Striatum S1HL M1 M2 (Caudate-Putamen) S1FL Cg1 S1DZ Cg2 cg S1BF IG cc LSD LV ec df TS SFi S2 CPu SFO vhc Pallidum GI BSTS D3V st ic (Globus pallidus) BSTMPM sm DI PVA LGP rf BSTMPI f AIP ADP Cl A14 IPACL 3V IPACM AC BSTLP DEn Pe acp VP Amygdala BSTMPL SLEA I Pir I SI VEn MPOM LPO MPOL mfb AAD MCPO CxA HDB MPA ACo AAV ox LOT SCh Paxinos, Franklin “The mouse brain in stereotaxic coordinates” (2001) Academic Press mouse brain  2. Nomenclature of the Basal Ganglia Striatum means “striped” or “gestreift”. This nucleus is “striped” by the axons that course through it. In humans, these axons bundle together to form the internal capsule. m Str atu iat In humans, the striatum is formed by m m Stri um nucleus caudatus and putamen. lidu lidu Pal Pal In mice, the striatum is one single mass often called caudate-putamen, caudoputamen or CP. The pallidum (“pale color”) is often called globus pallidus (“pale globe”) or GP. (Let us not forget that the caudate-putamen is the “dorsal striatum” and the globus pallidus is the “dorsal pallidum”.) CP CP GP GP Paxinos, Franklin “The mouse brain in stereotaxic coordinates” (2001) Academic Press 2. Caudoputamen (CP) and Globus Pallidus (GP) in the human brain  3 BASAL GANGLIA CONNECTIVITY  3. Connectivity of the Basal Ganglia: The Triple Projection + Thalamo-Cortical Loop 1) The entire isocortex projects topographically to the entire dorsal striatum (caudoputamen). This projection is GLUtamatergic, i.e. excitatory (e) and arises from the pyramidal cells of layer 5 and is a collateral of the descending axons of those neurons. 2) The dorsal striatum (caudoputamen) projects GABAergic, i.e. inhibitory (i) axons to the dorsal pallidum (globus pallidus). This projection is a collateral of the descending axons of those neurons, which end on the substantia nigra (compact and reticular). Larry W. Swanson (2012) “Brain Architecture: 3) The dorsal pallidum (globus pallidus) projects GABAergic, i.e. inhibitory (i) axons to the motor thalamus and to the substantia nigra. Because these axons are inhibitory and end on GABAergic neurons, they inhibit an inhibition, and therefore they are called “dis-inhibitory” (d). Understanding the Basic Plan” Oxford University Press 4) The entire thalamus projects topographically to the whole isocortex and to the whole dorsal striatum. 5) This “triple projection plus thalamo-cortical loop” repeats itself for the other subdivisions of striatum and pallidum (ventral, etc.).  3. Connectivity of the Basal Ganglia: The Triple Projection + Thalamo-Cortical Loop CORTEX STRIATUM PALLIDUM THALAMUS SUBSTANTIA NIGRA  4 BASAL GANGLIA FUNCTION 4. Function of CP and GP: motor control PLANNING: Intentional movements start with planning in the association cortex. PROGRAMMING: Cerebellum and basal ganglia program in parallel the motion sequence and inform the premotor cortex about these plans. EXECUTION: the premotor cortex passes this information to the motor cortex, which sends the appropriate instructions to the spinal alpha- motoneurons through the pyramidal pathway. CONTROL: control feedbacks from the CP and GP and cerebellum. CONTROL: sensory control feedbacks from the somatosensory pathways.  4. Function of CP and GP: direct and indirect control pathway Premotor, motor and somatosensory cortex send excitatory axons to the striatum. The striatum processes such CTX afferences and then sends inhibitory efferences back to the cortex (control feedback). These efferences form a direct and an indirect pathway. The direct pathway (through PALLIDUM, yellow arrows) dis-inhibits the thalamus, STR in this way stimulating the cortex and facilitating purposeful movement and PAL behavior. The indirect pathway (through PALLIDUM, Nucleus subthalamicus and TH Substantia Nigra, green arrows) inhibits the thalamus, in this way preventing it to SUBSTANTIA NIGRA stimulate the cortex and in this way preventing unwanted movements.  4. Function of CP and GP: role of the Substantia nigra The Substantia nigra PARS COMPACTA: activates the direct pathway inhibits the indirect pathway CTX If the dopaminergic neurons of the Substantia nigra Pars COMPACTA degenerate, the indirect pathway is not inhibited and the direct pathway is not activated. As a result, the thalamo-cortical pathway is inhibited… …and this leads to Parkinson’s Disease STR The Substantia nigra PARS RETICULARIS: inhibits the direct pathway PAL If the GABAergic neurons of the Substantia nigra Pars RETICULARIS degenerate, the thalamo- cortical pathway is not inhibited (too active)… TH …leading to spontaneous uncontrolled SUBSTANTIA NIGRA movements (Huntington’s disease, also called Huntington’s chorea, from the Greek word for “dance”, like choreography). End