Cognitive Neuroscience PSYC 768 Neuroscience 101

1. CognitiveNeurosciencePSYC 768Neuroscience 101 Raja Parasuraman

2. OverviewFunctional NeuroanatomyNeurophysiologyElements of Neurochemistry

3. Early Views of the Brain Galen Vesalius (1542) Leonardo da Vinci

4. Functional Neuroanatomy of Cognition Stimulus Response Anatomical subdivisions “Carving the mind at its joints”

5. Central (CNS) Brain Nervous System Organization Peripheral (PNS) Autonomic (ANS) Somatic (SNS) Spinal Cord Forebrain Midbrain Hindbrain Cortex Cortical Areas

6. Major Brain Structures Forebrain Midbrain and Hindbrain

7. The Brain is a 3-D Structure Forebrain (Neommamalian brain) II. Midbrain (Paleomammalian brain) III. Hindbrain (Reptilian brain) II and III sometimes collectively known as the “brainstem” http://www9.biostr.washington.edu/da.html (University of Washington Digital Anatomist Project)

8. The “Triune” Brain (Paul McLean) Increasing Functional Complexity Increasing Evolutionary Age

9. Development and Evolution “paleomammalian” “reptilian” “neomammalian” “Ontogeny recapitulates phylogeny”

10. The Hindbrain • Medulla • “Life support” functions • Regulation of respiration, muscle tension, etc. • If damaged • death • coma • Pons • Arousal and sleep (reticular formation) • Consciousness • If damaged • coma • sleep disorders

11. The Hindbrain (contd.) • Cerebellum • Coordination of movements (under cortical control) • Cognitive functions? • If damaged • Motor disorders

12. The Midbrain • Tectum • Superior colliculus • Eye movements • Inferior colliculus • Auditory orientation • Tegmentum • Reticular formation • Arousal and sleep • Substantia nigra • Motor initiation • If damaged: • Parkinson’s disease

13. The Forebrain • Basal ganglia • Monitoring of voluntary movements • If damaged: • Motor disorders (Huntingdon’s disease) • Thalamus • “Sensory relay center” • If damaged: • Attentional disorders

14. The Limbic Lobe • Cingulate gyrus • Hypothalamus • Amygdala • Hippocampus • Phylogenetically older than neocortex (allocortex and mesocortex) • These structures are involved in various aspects of emotional behavior

15. The 4 Major Cortical Lobes

16. Brodmann’s Areas (original)

17. Brodmann’s Areas (simplified functional)

18. Cortical Areas • Occipital Lobe • Primary visual cortex (Striate cortex; V1; Area 17) • Secondary visual areas (Extrastriate cortex; V2; Areas 18, 19) • Demarcated from the parietal and temporal lobes by the parieto-occipital sulcus

19. Cortical Areas • Parietal Lobe • Primary somatosensory cortex — Postcentral gyrus • Association areas play a role in attention and spatial processing • Demarcated from the frontal lobe by the central sulcus (or Rolandic fissure)

20. Cortical Areas • Temporal Lobe • Primary auditory cortex — Superior temporal gyrus (A1; Areas 41, 42) • Inferior temporal gyrus plays a role in visual object recognition • Medial temporal lobe (hidden in this view) plays a role in memory formation • Demarcated from the parietal lobe by the lateral sulcus (or Sylvian fissure)

21. Cortical Areas • Frontal Lobe • Primary motor cortex — Precentral gyrus (“Motor strip”: Area 4) • Homunculus in motor and somatosensory cortices

22. Cortical Areas • Frontal Lobe • Primary motor cortex — Precentral gyrus (“Motor strip”: Area 4) • Homunculus in motor and somatosensory cortices • Prefrontal cortex plays a role in higher cognitive functions • Dorsolateral prefrontal cortex • Anterior cingulate and medial prefrontal cortex • Orbitofrontal cortex

23. Cortical Regions http://www.med.harvard.edu/AANLIB/cases/caseNA/pb9.htm (Harvard Brain Anatomy and Pathology Project)

24. Cortex • Outer layer (“bark”) of forebrain • Approximately 3 mm thick and 2000 sq. cm in area • About 20 billion neurons, plus 200 billion glial cells • Convoluted — cortex is folded on itself • Gyrus (gyri) — protuding surfaces or bulges • Sulcus (sulci) —grooves or enfolded regions • Large sulci (fissures) • Longitudinal • Central (Rolandic) • Lateral (Sylvian) • Degree of convolution higher in primates, highest in humans

25. Cortical Layers • I: Molecular layer — mostly dendrites and long axons; few cell bodies • II: External granular layer – small pyramidal cells • III: Outer pyramidal layer — medium and large pyramidal cells; input from other cortical columns • IV: Internal granular layer — mostly granule cells; input layer from thalamus • V: Inner pyramidal layer — large pyramidal cells; motor output to spinal cord • VI: Multiform layer — mostly spindle cells

26. Cortical Columns (Vernon Mountcastle) • Oriented perpendicular to the cortical surface • 30-50 um diameter, spanning the 3 mm depth of the cortical layers • Each column contains approximately 100 neurons • Shape is quasi-hexagonal, because each cortical column is typically surrounded by six other columns • Columns function as “modules” A cortical column is a complex processing and distributing unit that links a number of inputs to a number of outputs via overlapping internal processing chains" (Mountcastle, 1998).

27. Modular Structure of Cortex Functional Columns Six Structural Layers Basic Information Processing Unit?

28. Neuronal Information Processing • Neuron to neuron communication • action potentials • postsynaptic potentials • Neurochemical innervation of cortex (subcortex)

29. Neuronal Conduction • Resting neuron membrane potential: - 70 mV • Active postsynaptic potential generated by input to neuron • Passive current flow through neuron • Depolarization (membrane potential ) • Hyperpolarization (membrane potential ) • Repolarization (return to resting membrane potential)

30. Neuronal Conduction (contd.) • If net potential at axon hillock > threshold, ion channels open (active process), and action potential generated (exchange of Na and K ions) • Na ions in: Rising phase of AP • K ions in: Falling phase of AP • AP duration approximately 1-2 ms (refractory period)

31. Neuronal Conduction: The Problem • Action potential decays over length of axon due to resistance and capacitance • Not a problem over short axonal distances (e.g., retina) but is for long distances (e.g., spinal motor neurons) • Resistance is reduced (and axonal speed increased) • However fat motor neurons needed to reach distant muscles would exceed width of spinal cord

32. The Solution: Myelin and Saltatory Conduction • Myelin (glial cell membrane) “insulates” axon and reduces resistance and increases speed of conduction • AP “regenerated” at gaps in myelin (Nodes of Ranvier) where ion channels are found • Saltatory conduction (“jumps”) represents a tradeoff between signal loss due to axonal length and speed

33. Saltatory Conduction

34. Myelin and Saltatory Conduction (contd.) • Unmyelinated neurons are the fastest in the nervous system, but can only conduct over short distances • Myelinated neurons are slower, but can conduct over longer distances (~ 100 m/s) Unmyelinated (no Nodes of Ranvier), fastest, short distance Myelinated (many nodes), slow, longer distance Myelinated (few nodes), faster, shorter distance

35. Synaptic Transmission • Synapse: Gap between axon of one neuron and dendrite (or cell body) of another cell • presynaptic neuron • postsynaptic neuron • Synaptic transmission involves communication across the synapse from one neuron to another • chemical • electrical

36. Synaptic Transmission (contd.) • Chemical transmission involves • voltage-gated Ca2+ ion channels in the presynaptic neuron • receptors (specialized ion channels) in the postsynaptic neuron

37. Chronology of Events at Synapse • Action potential arrives at axon terminal • Vesicles containing neurotransmitter fuse with presynaptic membrane (with help of Ca2+) • Neurotransmitter released into synaptic cleft (gap) • Neurotransmitter diffuses across cleft and binds with postsynaptic receptors

38. Chronology of Events at Synapse (and beyond) • Binding (lock and key) of NT and receptor results in postsynaptic potential (PSP) • Depending on postsynaptic receptor, the PSPs can be excitatory or positive (EPSP) or inhibitory or negative (IPSP) • Spatial and temporal summation of EPSPs and IPSPs at axon hillock leads to action potential, and so the process of neuronal communication continues Action potential: On or off — a digital signal PSPs: Can have multiple values, positive or negative — an analog signal

39. Discovery of The First Neurotransmitter • Acetylcholine (ACh) • Discovered by Otto Loewi (1924) • Vagus nerve stimulation of heart muscle • Chemical stimulation of second heart • Henry Dale showed that ACh is also involved at the neuromuscular junction • Curare (as in poison darts) occupies receptor sites in muscles, hence preventing ACh to work and causing paralysis

40. Routes to Paralysis and Intoxication

41. We now understand the microstructure of neurotransmitter receptors

42. Classes of Neurotransmitters • Acetylcholine • Amino acids • excitatory • glutamate • aspartate • inhibitory • gamma-aminobutyric acid (GABA) • glycine • taurine4 • Biogenic amines • serotonin • histamine • catecholamines • dopamine • norepinephrine • Neuropeptides • Over 50 known Underlined NTs have been linked to different aspects of cognitive functioning

43. Key Historical Figures Sir Charles Sherrington 1857-1952 Sir Henry Dale 1875-1968 Otto Loewi 1873-1951 All Nobel Prize Winners Eric Kandel 1934 - present Sir John Eccles 1903-1997

44. Internet Resources • www.cogneurosociety.org (Cognitive Neuroscience Society) • www.sfn.org (Society for Neuroscience) • http://www.humanbrainmapping.org/ (Organization for Human Brain Mapping) • http://www9.biostr.washington.edu/da.html (University of Washington Digital Anatomist Project) • http://www.med.harvard.edu/AANLIB/home.html (Harvard Brain Anatomy and Pathology Project) • http://www.univie.ac.at/anatomie2/plastinatedbrain/main.html (The Plastinated Brain) • http://www-medlib.med.utah.edu/kw/sol/sss/subj2.htmlUniversity of Utah Medical School)