Learning and Memory

HIGHER FUNCTIONS OF BRAIN-Learning and Memory

1. LEARNING AND MEMORY Dr. Ranadhi Das MD PGT [email protected]

2. LEARNING AND MEMORY Learning- Reflex Learning- Non Associative- Habituation Sensitization Associative- Classical Conditioning Operant Conditioning Incidental Learning Memory- Physiologically On The Basis Of How Information Is Stored & Recalled Implicit Memory. Procedural Memory Priming Explicit Memory Semantic Memory Episodic Memory Depending Upon Permanency Of Storage Short Term. Intermediate Long Term. Long Term Consolidation Encoding Retrieval Applied Aspects Substances Facilitate Memory And Learning Addiction Amnesia Antegrade Retrograde Senile Dementia Alzheimer Disease Concept Of Dominant Hemisphere

3. LEARNING & MEMORY Learning – The ability to alter behavior on the basis of experience. Memory – Acquisition , storage & retrieval of sensory information. Ability to recall past events at the conscious or unconscious level. Thought – A thought result from a pattern of stimulation of many parts of the nervous system at the same time & in a definite sequence, probably involving the cerebral cortex, thalamus, limbic system, upper reticular formation of brain stem. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 3

4. LEARNING . Reflex learning. Associated with immediate behavior change. Incidental learning. Behavior change not immediate But person gets information from sensory inputs & develop potential to behave differently. Saturday, July 29, 2017 4 HIGHER FUNCTIONS OF BRAIN.

5. REFLEX LEARNING. Non- associative . Person learns about properties of single stimulus when repeatedly exposed to same stimulus. Associative. Person learns about relationship between two stimuli or a stimulus & behavior. Saturday, July 29, 2017 5 HIGHER FUNCTIONS OF BRAIN.

6. NON- ASSOCIATIVE . Habituation Decrease in response to benign stimulus when stimulus presented repeatedly. Sensitization. Increase in response to benign stimulus when stimulus presented repeatedly with an pleasant or unpleasant stimuli. Saturday, July 29, 2017 6 HIGHER FUNCTIONS OF BRAIN.

7. First time it evokes a novel response (orientation response or what is it response) Evokes less & less response when repeated Subject becomes habituated to the stimulus & ignores it Habituation If a stimulus is repeated many times

8. Habituation Example New clock in the room. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 8

9. Cellular basis of Habituation. Given by KANDEL & his colleague . The brain learn to ignore matter of less important. This result from inhibition of the synaptic pathway. Repeated stimulus. Gradual inactivation of Ca +2 influx at axon endings. Decrease intracellular Ca +2 Neurotransmitter release at synapses. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 9

10. Sensitization The type of sensory information which cause pleasure, pain or interest are stored in brain by facilitation of synaptic pathway. Example- Spanking. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 10

11. Cellular basis of Sensitization. Given by KANDEL & his colleague. Repeated stimulus . Ca+2 mediated changes in adenylyl cyclase Increased production of cAMP neurotransmitter release at synapses. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 11

12. Due to Presynaptic Facilitation by third interneuron --- Facilitatory neuron. which releases SEROTONIN. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 12 Sensitization Post synaptic neuron Pre synaptic ending

13. ASSOCIATIVE LEARNING. Classical conditioning. Learning relationship between two stimuli. Pavlovian conditioning. Operant conditioning. Learning relationship between special behavior with a reinforcement event. Instrumental or Trial & error conditioning. Saturday, July 29, 2017 13 HIGHER FUNCTIONS OF BRAIN.

14. CLASSICAL CONDITIONING. It is a cortical phenomenon. These are example of higher learning. Conditioned reflex is Reflex response to a stimuli that previously elicited little or no response Acquired by repeatedly pairing given stimulus with another stimulus which normally produces the response. Thus temporal association made between neutral conditioned stimulus (CS) & unconditioned stimulus. (US) It depends upon formation of new functional connections in CNS. Reinforcement -- CS SHOULD FOLLOWED BY US Saturday, July 29, 2017 14 HIGHER FUNCTIONS OF BRAIN.

15. CLASSICAL CONDITIONING. Saturday, July 29, 2017 15 HIGHER FUNCTIONS OF BRAIN.

16. Unconditioned reflex were present in all animal. Inborn reflexes Centre in spinal cord and medulla. Example- Postural reflexes for maintaining body posture, salivary reflex and sexual reflexes. Conditioned reflex are acquired reflex Certain conditions are required to fulfill it. Centre- cerebral cortex In case of Pavlov experiment the ringing of bell is a neutral stimulus. It will not cause salivation in any dog, unless trained. For establishment of a conditioned reflex fresh connection are established in the nervous system between the auditory center and center of salivation.

17. Pre-requisites for development of conditioned reflex. Alertness & good health . Should not be harmful Reinforcement - once CS is established the pairing of conditioned and unconditioned stimulus is done at intervals. If you go on ringing the bell and that’s not followed by giving meat, then no salivation occurs. This abolition of reflex is known as Internal Inhibition . If the animal is disturbed by an external stimulus immediately after CS is applied, the CS may not occurs, Known as External inhibition . CS should precede on US Summation - If few CS are summated the response is better. Discrimination - Animal can discriminate between 2 different stimuli. Eg . Change of sound frequency of bell cause internal inhibition. Linking - Animal learns to associate 2 different process. Saturday, July 29, 2017 17 HIGHER FUNCTIONS OF BRAIN.

18. An immense number of somatic, visceral and other neural changes can be made to occur as conditioned reflex responses. Conditioning of visceral responses is often called Biofeedback . The changes include heart rate alteration and BP changes. Conditioned decrease in BP has been advocated for treatment of HTN.

19. OPERANT CONDITIONING. Reward conditioning. Naturally occurring response is strengthened by positive reinforcement (reward) Adversive conditioning. Naturally occurring response is Weakened by Negative reinforcement (Punishment) It is to avoid an unpleasant event Saturday, July 29, 2017 19 HIGHER FUNCTIONS OF BRAIN.

20. Experiment to demonstrate Operant conditioning. Saturday, July 29, 2017 20 HIGHER FUNCTIONS OF BRAIN.

21. Experiment to demonstrate Operant conditioning. Positive Reinforcement – pressing a lever is associated with positive reinforcement, reward i.e. food. Negative Reinforcement – pressing a lever is associated with Negative reinforcement, punishment i.e. electric shock. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 21

22. MEMORY. Memory – Acquisition , storage & retrieval of sensory information Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 22

23. TYPES OF MEMORY. Physiologically on the basis of how information is stored & recalled. Implicit memory. Explicit memory. Depending upon permanency of storage. Short term. Intermediate long term. Long term. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 23

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25. TYPES OF MEMORY. Implicit memory . Non-declarative / reflexive memory. How to perform something. Not associated with awareness not involve processing in hippocampus. Explicit memory . Declarative / Reconition memory Factual knowledge of people, places & things. Associated with awareness ,Involve processing in hippocampus. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 25

26. IMPLICIT MEMORY. How to perform something. Does not depend on conscious process. Includes motor skills, habits, behavioral reflexes & learning procedure & rules. Unconsciousness & automatic Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 26

27. Implicit memory – reflexive learning. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 27

28. EXPLICIT MEMORY. Declarative / Recognition memory Factual knowledge of people, places & things. Associated with awareness ,Involve processing in hippocampus. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 28

29. EXPLICIT MEMORY. SEMANTIC MEMORY About knowledge of objects, facts and concepts. Words & their meanings. EPISODIC MEMORY Memory of events & personal experience. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 29

30. SEMANTIC MEMORY. Storage of semantic memory In distributed fashion in different association cortices. Visual memory Auditory memory Somatosensory memory . Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 30

31. TYPES OF MEMORY

32. Damage to cortical area – loss of specific information Associative Visual Agnosia – posterior parietal cortex damage – can identify but cannot name the objects. Appreciative Visual Agnosia – posterior occipital lobe damage – can name the objects but cannot draw Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 32

33. EPISODIC MEMORY. Storage of Episodic Memory In association area of prefrontal cortex. With other areas of neo-cortex for collection of information Damage – Amnesia. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 33

34. MECHANISM OF MEMORY. Explicit memory. Short term memory. Neural substrate for encoding of memory. Intermediate long term. Long term . Consolidation of memory. Storage of memory. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 34

35. MECHANISM OF SHORT TERM MEMORY Theory of reverberating neurons- Caused by continual neural activity resulting from nerve signals that travel round and round in a temporary trace through a circuit of reverberating neurons. Presynaptic facilitation or inhibition- Occurs at synapses that lie on the presynaptic terminals, not on the subsequent neuron. The neurotransmitter secreted at such terminals frequently cause prolonged facilitation or inhibition. Synaptic Potentiation- It can enhance synaptic conduction. Accumulation of large amount of Ca in presynaptic terminals due to train of impulses passing through. When amount of Ca become greater than the mitochondria can absorb  causes prolonged presynaptic release of NT.

36. Working memory. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 36

37. MECHANISM OF INTERMEDIATE LONG TERM MEMORY Intermediate Memory due to temporary physical or chemical change in pre or post synaptic membrane. Still labile until becomes long term by process called – Consolidation. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 37

38. Mechanism of intermediate Long term memory Post synaptic neuron Pre synaptic ending C B A

39. Mechanism of intermediate Long term memory Mechanism for Habituation- Results from progressive closure of Ca+2 channel of presynaptic terminal membrane V ery small entry of Ca+2  very Little amount of NT released. Mechanism for Facilitation- Stimulation of facilitator terminal B at the same time of sensory terminal A Serotonin released by the sensory terminal B It acts on the serotonin receptor in sensory terminal A membrane Receptor activate enzyme Adenylyl cyclase at membrane Formation of cAMP inside A cAMP activates Protein Kinase

40. Protein kinase cause phosphorylation of a protein that is a part of K+ channel at sensory terminal A This blocks the channel for K+ conductance ( mins to Wks ) Lack of K+ conductance cause greatly prolonged AP in terminal A ( Outflux of K+ is necessary for transmission of AP) Prolonged AP causes prolonged activation of Ca+2 channel Tremendous quantity of Ca+2 enter into the sensory terminal A Ca+2 result in increased NT release, thereby greatly facilitating synaptic transmission.

41. LONG TERM MEMORY The difference is only in degree Result in actual structural changes ( physical restructuring of synapses) , instead of chemical changes only Changes due to DNA which replicate the protein in presynaptic neurons Also responsible for development of memory trace. The changes are- Increase in no. of vescicles release sites for secretion of NT  increase NT release by exocytosis Increase in no. of transmitter vescicles Increase in no. of presynaptic terminals In contrast to working memory long term memory was improved with exposure of the subject to an enriched environment. This induce dramatic anatomical changes in cerebral cortex, hippocampus and cerebellum of brain. The ability of a neural tissue to change because of its activation is known as plasticity.

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43. MECHANISM OF LONG TERM MEMORY Consolidation of Memory Rehearsal of the same information again and again in the mind accelerate and potentiate the degree of transfer of short term memory to long term memory. For mild – 5-10 min For strong – 1 or more hour. If this time not given – retrograde amnesia E.g. – Precise time of sleep Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 43

44. PROCESS OF CONSOLIDATION Expression of genes Synthesis of new proteins Structural changes . Increase in no of vesicle release sites No of vesicles No of synaptic terminals Change in shape or no of postsynaptic spines Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 44

45. CODYFYING THE MEMORIES DURING CONSOLIDATION Similar information is recalled from the memory storage bin and used to help process the new information. Parts involved- Hippocampus Thalamus Prefrontal cortex Amygdala neocortex

46. RETRIEVAL OF MEMORY. Components. Attentional control system. Rehearsal system. Articulatory loop. Visuospatial sketch pad. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 46

47. Neural substrate for encoding of memory. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 47

48. MECHANISM OF LONG TERM POTENTIATION(LTP) It involves protein synthesis and growth of presynaptic and postsynaptic neurons and their connections. LTP occurs in many parts of the brain. Studied on synapses of hippocampus, connection of pyramidal cell in CA 3 and CA 1 region via Schaffer Collateral.

49. At the membrane potential , Glutamate release from presynaptic nu. Bind both NMDA and Non-NMDA (AMPA) receptors on postsynaptic nu Mg+ blocks NMDA receptor so Na +, K + can flow only through AMPA receptors Mg+ expel from NMDA due to high frequency tetanic stimulation of presynaptic nu. Ca+2 influx at postsynaptic neuron Activation of Ca+2/ calmodulin Kinase, Pr. Kinase C, Tyrosin Kinase (Together induce LTP) Ca+2/ calmodulin complex phosphorylate AMPA receptors Increased conductance, more and more of these receptors move to synaptic cell membrane from cytoplasmic storage site When LTP induced, chemical signal NO released by postsynaptic nu and pass retrograde to presynaptic neur. And produce long term increase in Glutamate release

50. MECHANISM OF LONG TERM POTENTIATION Pre synaptic ending Post synaptic neuron

51. APPLIED ASPECT. Drugs facilitating learning & memory. Common CNS stimulant Caffeine, amphetamine, Physostigmine ( Inhibit acetylcholinesterase, prevent breakdown of Ach) Nicotine ( stimulate nicotinic cholinergic receptors) Pemoline ( stimulate RNA synthesis) Mechanism of action. By facilitating consolidation of energy. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 51

52. ADDICTION Morphine Amphetamine Cocaine Heroin Nicotine Alcohol All these produces Dopamine on the limbic system on nu. Accumbens All stimulate reward area.

53. AMNESIA . Antegrade . Inability to establish new long term memories Mostly in lesions involving hippocampus. Retrograde – Inability to recall past memories. Amnesia greater for recent past than remote past. Lesions involving temporal lobe (Temporal lobe syndrome) Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 53

54. SENILE DEMENTIA. Syndrome in elderly people characterized by progressive impairment of memory & cognitive capacity. Causes – Alzheimer’s disease, Cerebrovascular disease, Parkinsonism, Lewy body dementia, Prion disease Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 54

55. Alzheimer’s disease. Senile dementia Prototypical neurodegenerative disease. Degeneration of pathways from septal region of the forebrain to the hippocampus. Affecting 15-25% people over 65 Cholinergic neurons cease functions. Associated with decrease release of Ach in some area of brain. Loss of postsynaptic neurons. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 55

56. CHARACTERISTIC FEATURES. Loss of recent memory. Impairment in other areas of cognition – language, problem solving, judgment, calculation, attention. Psychiatric symptoms Loss of spatial orientation. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 56

57. CONCEPT OF DOMINANT HEMISPHERE. Interpretive functions of Wernicke’s area, Angular gyrus & Frontal motor speech area – more developed in Dominant hemisphere . Saturday, July 29, 2017 57 HIGHER FUNCTIONS OF BRAIN.

58. CONCEPT OF DOMINANT HEMISPHERE 95% left hemisphere is dominant. Wernicke’s area in Non-dominant is concerned with emotional content, intonation of spoken language, understanding & interpreting non-verbal, visual & auditory experiences as interpretation of Music. Saturday, July 29, 2017 HIGHER FUNCTIONS OF BRAIN. 58

59. CONCEPT OF CATEGORICAL & REPRESENTATIONAL HEMISPHERE. Functions allotted to left hemisphere in right handed person. Right hand control. Spoken language. Written language. Mathematical skills. Scientific skills. Reasoning. Functions allotted to right hemisphere in right handed person. Left hand control. Music awareness. Three dimensional awareness. Art awareness. Insight. Imagination. Saturday, July 29, 2017 59 HIGHER FUNCTIONS OF BRAIN.

60. Saturday, July 29, 2017 60 HIGHER FUNCTIONS OF BRAIN. Thank You