BSC 343 2009 Ex4 Lect3.ppt

The Basal Ganglia BSC 343 Nov. 17, 2009 Exam 4 ? Lect 3 Grading Undergraduate Students: Total points = 100. Four exams, each covering approximately one fourth of the course material, are worth 22 points each. Exam 4 is therefore not a comprehensive final exam. Four written assignments (3pts each) will be assigned during the semester. Graduate Students: Total points = 122. Graduate students will be required to take the same four exams as undergraduate students (22 points each) and complete the same written work (12 points). Additionally, a paper worth 22 points will be assigned on a topic related to neurobiology. The paper will be 10 pages double spaced pages plus 15 primary references. A primary reference is a manuscript describing, for the first time, results from original experiments and published in a peer-reviewed journal. A primary reference is not a review article, book, book chapter, Web Page, etc. Topics are open to any area of neurobiology, but please consult the instructor before finalizing your topic. The paper is due the last day of class ? Thurs. Dec. 3, 2009 THIS PAPER IS NOW OPEN TO UNDERGRADUATES; HOWEVER, YOU MUST TALK TO ME BEFORE THANKGIVING BREAK ? Fri. Nov. 20, 2009 Homework Assignment #4 DUE Dec. 3 @ 2PM Read and write a summary (~1-2 pages) on Gould et al., Nature Neuroscience, 1999. Include the following information: ?introduction? (why they did the experiments) ?methods? (how they did the experiments) ?results? (what they found) ?discussion? (the importance of what they found) Additionally, explain what type of memory is being investigated and the behavioral paradigms used to study this form of memory COMPLETE SENTENCES AND PARAGRAPHS BLACK INK ON WHITE PAPER (NO LINES) HAND WRITTEN OR TYPED (COMPUTER) Learning increased the number of BrdU labeled cells (red; a-b) TOAD-64 (neuronal marker) GFAP (glial marker) new cells look like immature granule cells (green; c), not glia (green; d) Hippocampally-dependent place (spatial) learning increased cells in the DG, but not basal ganglia-dependent cued learning or stress Hippocampally-dependent trace conditioning increased cells in the DG, but not hippocampally-independent delay conditioning Procedural memory, also known as implicit memory or unconscious memory, is the long-term memory of skills and procedures, or "how to" knowledge (procedural knowledge). Procedural memory is often not easily verbalized, but can be used without consciously thinking about it; procedural memory can reflect simple stimulus-response pairing or more extensive patterns learned over time. Examples of procedural learning are learning to ride a bike, learning to touch type, learning to play a musical instrument or driving a car. Procedural memory can be very durable. Damage to the cerebellum and the basal ganglia seems to particularly affect procedural learning. http://en.wikipedia.org/wiki/Declarative_memory Basal ganglia function Involved in processing (controlling and coordinating) motor movements ie. driving a car Plasticity in the BG motor learning patterns of motor activity motor-response learning primate non-primate 1. Striatum caudate medial striatum putamen lateral striatum 2. Globus GPi EPN (MGP) Pallidus GPe GP (LGP) 3. Substantia SNr same Nigra SNc same (DA input) 4. Subthalamic STN same Nucleus Input nucleus - striatum Output nuclei - SNr/GPi EPN - entopeduncular nucleus GPi - internal segment of the globus pallidus GPe - external segment of the globus pallidus SNr - substantia nigra pars reticulata SNc - substantia nigra pars compacta Basal Ganglia Components CORTEX STRIATUM SNr/GPi STN THAL GPe SNc DA DA modulation BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA BLUE = THALAMUS BLACK = HYPOTHALAMUS RED = CAUDATE NUCLEUS YELLOW = LENTICULAR NUCLEUS PURPLE = HIPPOCAMPUS GREEN = AMYGDALA DA modulation HUMAN (SNr) RAT (SNr) Globus Pallidus or Pallidum primate non-primate GPi - internal segment or medial pallidum Entopeduncular nucleus or medial globus pallidus Globus Pallidus or Pallidum primate non-primate GPi - internal segment or medial pallidum Entopeduncular nucleus or medial globus pallidus Globus Pallidus or Pallidum primate non-primate GPe - external segment or lateral pallidum Lateral globus pallidus Globus Pallidus or Pallidum primate non-primate GPe - external segment or lateral pallidum Lateral globus pallidus HUMAN (STN) RAT (STN) HUMAN (Thalamus) RAT (Thalamus) RAT (striatum) DL DM BG Neurotransmitters Glutamate - excitatory GABA - inhibitory Dopamine - modulatory STRIATUM STN DA +glut +glut GABA- GABA- GABA- GABA- +glut SNr/GPi THAL GPe SNc CORTEX BG Circuitry Output nuclei (SNr/GPi) are tonically active and tonically inhibit (GABA) the thalamus. Thereby, modulating thalamic activation (glut) of the cortex. This release of GABA from the output nuclei is regulated by two pathways (direct and indirect). Two major pathways of the BG: Direct pathway/striatonigral Indirect pathway/striatopallidal STRIATUM STN DA +glut +glut GABA- GABA- GABA- GABA- +glut SNr/GPi THAL GPe SNc CORTEX DIRECT INDIRECT ?BASIC? BG Circuitry: Direct Pathway 1. cortex (glut) activates striatonigral (direct pathway) neurons 3. which decreases inhibition (?disinhibition?) of SNr/GPi (GABA) to the thalamus 2. striatonigral neurons (GABA) inhibit the SNr/GPi 4. therefore, the thalamus activates the cortex (glut) END RESULT: cortex is further activated ?positive feedback loop? STRIATUM GABA- GABA- SNr/GPi THAL CORTEX DIRECT 1. 2. 3. 4. +glut +glut ?BASIC? BG Circuitry: Indirect Pathway 1. cortex (glut) activates striatopallidal (indirect pathway) neurons 2. striatopallidal neurons (GABA) inhibit the GPe 3. which decreases inhibition (?disinhibition?) of the STN (GABA) 4. therefore, the STN (glut) activates the output nuclei (SNr/GPi) leads to increased inhibition (GABA) of the thalamus 6. as a result the thalamus releases less glut to the cortex END RESULT: cortical activation is decreased - ?negative feedback loop? STRIATUM STN +glut +glut GABA- GABA- GABA- +glut CORTEX SNr/GPi THAL GPe INDIRECT 1. 2. 3. 4. 5. 6. DA modulation DOPAMINE NEUROANATOMY RAT HUMAN Substantial nigra pars compacta ? DA innervation to the dorsal striatum (caudate/putamen) Ventral tegmental area - DA innervation to the ventral striatum (nucleus accumbens) Nucleus accumbens ? important in ?reward? learning (primary rewards, i.e., food and sex) Medial forebrain bundle group of DA neuron fibers rat ~ 10,000 fibers human >100,000 fibers DA neurons fire in 2 modes: 1.) Tonic signaling 2.) Phasic signaling DA nerve fibers Asynchronous firing Low frequency firing Constant (steady-state) Maintains basal level of DA Tonic DA Signaling I time DA nerve fibers Asynchronous firing Low frequency firing Constant (steady-state) Maintains basal level of DA Tonic DA Signaling I time DA nerve fibers Asynchronous firing Low frequency firing Constant (steady-state) Maintains basal level of DA Tonic DA Signaling I time DA nerve fibers Asynchronous firing Low frequency firing Constant (steady-state) Maintains basal level of DA Tonic DA Signaling I time I time Synchronous firing High frequency firing - bursts Pulsatile Reward signal Phasic DA Signaling DA transient DA nerve fibers I time Synchronous firing High frequency firing - bursts Pulsatile Reward signal Phasic DA Signaling DA transient DA nerve fibers I time Synchronous firing High frequency firing - bursts Pulsatile Reward signal Phasic DA Signaling DA transient DA nerve fibers DOPAMINE, LEARNING & ADDICTION Phasic DA signaling Increase in DA transients Synaptic plasticity primary rewards (i.e., food, sex) (modified from Cheer et al., 2007) DRUGS Medium spiny neuron Make up 95% of neurons in striatum DA activates striatonigral neurons via D1 receptor activation (Na+ entry into the cell) END RESULT: more glut is released from the thalamus to the cortex DA facilitates the activity of the direct pathway DA modulation - direct pathway striatonigral neurons (GABA) inhibit the SNr/GPi which decreases inhibition (?disinhibition?) of SNr/GPi (GABA) to the thalamus STRIATUM CORTEX SNr/GPi THAL DA SNc GABA- +glut GABA- D1 DA modulation - indirect pathway DA inhibits striatopallidal neurons via D2 receptor activation (K+ exiting the cell) END RESULT: more glut is released from thalamus to the cortex DA inhibits the activity of the indirect pathway decreases the activity of striatopallidal neurons (GABA) inhibiting the GPe more GABA is released from the GPe to the STN less glut is released from the STN to the SNr/GPi less GABA is released from SNr/GPi to the thalamus STRIATUM STN DA CORTEX SNr/GPi SNc +glut +glut GABA- +glut GABA- GABA- GPe D2 THAL Hyperdirect pathway 1. cortex (glut) activates STN 2. STN (glut) activates output nuclei (SNr/GPi) 3. leads to increased inhibition (GABA) of the thalamus 4. as a result the thalamus releases less glut to the cortex CORTEX SNr/GPi STN THAL +glut +glut GABA- +glut HYPERDIRECT 1. 2. 3. 4. Summary of pathways Direct pathway - ? glut to cortex Indirect pathway - ? glut to cortex Hyperdirect pathway - ? glut to cortex DA/direct pathway - ? glut to cortex DA/indirect pathway - ? glut to cortex Balance of all of these leads to modulation (?scaling?) of motor movements CORTEX STRIATUM SNr/GPi STN THAL GPe SNc DA DIRECT INDIRECT HYPERDIRECT +glut Basal ganglia are thought to facilitate the selection of motor programs and suppress competing motor programs that could interfere with the timely expression of sensory-driven or goal-oriented behavior.