http www pbs orgsaf1402videowatchonline htm Neuroscience Exploring the

http: //www. pbs. org/saf/1402/video/watchonline. htm Neuroscience: Exploring the Brain, 3 e Chapter 24: Memory Systems http: //www. pigeon. psy. tufts. edu/asc/Mizum ori/Default. htm Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Introduction • Learning: Lifelong adaptation to environment • Several similarities between experience dependent brain development and learning – Similar mechanisms at different times and in different cortical areas • Memories range from stated facts to ingrained motor patterns • Anatomy: Several memory systems – Evident from brain lesions Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Types of Memory and Amnesia • Learning: Acquisition of new information • Memory: Retention of learned information • Declarative memory (explicit) – Facts and events • Nondeclarative memory (implicit) – Procedural memory- skills, habits Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Types of Memory and Amnesia • Long-Term, Short-Term, and Working Memory Sensory information Short-term memory Consolidation Long-term memory Short-term memory Sensory information Consolidation Long-term memory Time – Working memory: Temporary information storage requiring rehearsal Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Types of Memory and Amnesia • Amnesia – Retrograde amnesia: Forget things you already knew – Anterograde amnesia: Inability to form new memories Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Search for the Engram • Lashley’s Studies of Maze Learning in Rats Engram:

The Search for the Engram • Hebb and the Cell Assembly – External events are represented by cortical cells – Cells reciprocally interconnected reverberation – Active neurons—cell assembly • Consolidation by “growth process” • “Fire together, wire together” – Hebb and the engram • Widely distributed among linked cells in the assembly • Could involve neurons involved in sensation and perception Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Search for the Engram • Hebb’s Cell Assembly and Memory Storage Hypothesis •

The Search for the Engram • Localization of Declarative Memories in the Neocortex – Inferotemporal Cortex (area IT), higher-order visual area in macaques – Lesion impairs discrimination task despite intact visual system at lower levels – Disruption of memory or visual pattern recognition? Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Search for the Engram • Localization of Declarative Memories in the Neocortex – At first, all cells respond to newly presented faces the same amount – With repeated exposures, some faces evoke a greater response than others - i. e. , cells become more selective (Adapted from Rolls et al. , 1989 Exp Brain Res 76: 153 -164, Figure 1. ) Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Search for the Engram • Electrical Stimulation of the Human Temporal Lobes – Temporal lobe stimulation • Different from stimulation of other areas of neocortex – Penfield’s experiments • Stimulation -> Sensations like hallucinations, recall past experiences – Temporal lobe: Role in memory storage – Caveat: Minority of patients, all had epilepsy Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Temporal Lobes and Declarative Memory • The Effects of Temporal Lobectomy (HM) Copyright

The Temporal Lobes and Declarative Memory • The Medial Temporal Lobes and Declarative Memory

The Temporal Lobes and Declarative Memory • The Effects of Temporal Lobectomy (HM) – Removal of temporal lobes had no effect on perception, intelligence, personality – Anterograde amnesia so profound could not perform basic human activities (and partial retrograde amnesia) – Never recognized Brenda Milner, who had studied him for nearly 50 years – Impaired declarative memory, but spared procedural memory (mirror drawing) http: //www. pbs. org/saf/1402/video/watchonline. htm http: //youtu. be/Soxs. MMV 538 U Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Memory capacity: Jill Price http: //youtu. be/Soxs. MMV 538 U Copyright © 2007 Wolters

The Temporal Lobes and Declarative Memory • The Medial Temporal Lobes and Declarative Memory – Information flow through medial temporal lobe Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Temporal Lobes and Declarative Memory • The Medial Temporal Lobes and Memory Processing (Cont’d) – DNMS: Delayed non-match to sample – Medial temporal lobe structures: Important for memory consolidation Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Temporal Lobes and Declarative Memory • The Medial Temporal Lobes and Memory Processing (Cont’d) – Effect of medial temporal lobe lesions on DNMS – Recognition memory Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Temporal Lobes and Declarative Memory • The Diencephalon and Memory Processing – Brain regions associated with memory and amnesia outside the temporal lobe Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Temporal Lobes and Declarative Memory • The Diencephalon and Memory Processing – Radio technician 1959 accidentally stabbed through left dorsomedial thalamus with fencing foil • Less severe but like HM; anterograde and some retrograde amnesia – Korsakoff’s Syndrome: Alcoholics - thiamin deficiency • Symptoms: Confusion, confabulations, severe memory impairment, apathy, abnormal eye movements, loss of coordination, tremors • Lesions to dorsomedial thalamus and mamillary bodies – Treatment: Supplemental thiamin Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Temporal Lobes and Declarative Memory • Memory Functions of the Hippocampus – Hippocampal responses to old (familiar) and new stimuli Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Temporal Lobes and Declarative Memory • Radial arm maze (a) – (b) Normal rats go down each arm for food only once, but with hippocampal lesions revisit arms already explored – (c) Normal and lesioned rats learn which arms are baited and avoid the rest, but still revisit arms (don’t remember that they have already taken the food from the arm). Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

http: //www. pigeon. psy. tufts. edu/asc/Mizumori/D efault. htm The Temporal Lobes and Declarative Memory http: //youtu. be/PGHRDc. PKio 8 http: //youtu. be/lf. NVv 0 A 8 Qv. I • Spatial Memory and Hippocampal Place Cells • Morris water maze: requires NMDA receptors in hippocampus. • Place cells fire when animal is in a specific place. • Dynamic: Place fields develop as rat becomes familiar with environment • Do ‘Place cells’ really code for place? Linear maze; restraint experiments Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Place cells Grid Cells Copyright © 2007 Wolters Kluwer Health | Lippincott Williams &

Place field: http: //youtu. be/PGHRDc. PKio 8

Place cell activity http: //www. youtube. com/watch? v=lf. NVv 0 A 8 Qv. I&feature=youtu. be

http: //www. pigeon. psy. tufts. edu/asc/Mizumori/D efault. htm The Temporal Lobes and Declarative Memory http: //youtu. be/PGHRDc. PKio 8 http: //youtu. be/lf. NVv 0 A 8 Qv. I • Spatial Memory and Hippocampal Place Cells • Morris water maze: requires NMDA receptors in hippocampus. • Place cells fire when animal is in a specific place. • Dynamic: Place fields develop as rat becomes familiar with environment • Do ‘Place cells’ really code for place? Linear maze; restraint experiments. Relational hypothesis Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Causal role of hippocampal cell activity in establishing associative memories c-fos-t. TA transgenic mice: promoter of the c-fos gene drives the expression of the tetracycline transactivator (t. TA) to induce expression of a gene downstream of the tetracycline-responsive element (TRE) (8– 12). Inject AAV 4 virus encoding TRE-Ch. R 2 -m. Cherry into the DG or CA 1 of c-fos-t. TA animals Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Temporal Lobes and Declarative Memory • Spatial Memory and Hippocampal Place Cells – PET imaging in human brain related to spatial navigation of a virtual town – Single neuron recording (Epilepsy patients)- ‘place cells’ exist in human hippocampus Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Striatum and Procedural Memory • Caudate nucleus + Putamen = Striatum – Lesions to striatum disrupt procedural memory (habit learning) – Standard radial arm maze depends on hippocampus – Modified radial arm maze, with lighted arms, depends on striatum; learn assoc. (food at lighted arms). • Damaged hippocampal system: Degraded performance on standard maze task • Damaged striatum: Impaired performance of the modified task; ‘Double dissociation’ of lesion site and behavioral deficit. Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Striatum and Procedural Memory • Habit Learning in Humans and Nonhuman Primates – Parkinson’s patients show that human striatum plays a role in procedural memory Declarative Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Neocortex and Working Memory • The Prefrontal Cortex and Working Memory – Primates have a large frontal lobe – Function of prefrontal cortex: self-awareness, capacity for planning and problem solving Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Neocortex and Working Memory Copyright © 2007 Wolters Kluwer Health | Lippincott Williams

The Neocortex and Working Memory • The Prefrontal Cortex and Working Memory – Working

The Neocortex and Working Memory • The Prefrontal Cortex and Working Memory – Wisconsin

The Neocortex and Working Memory • The Prefrontal Cortex and Working Memory (Cont’d) – Imaging Working Memory in the Human Brain – Six frontal lobe areas show sustained activity correlated with working memory – Blue: Facial memory – Green: Facial and spatial memory Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Neocortex and Working Memory • Lateral Intraparietal Cortex (Area LIP) and Working Memory – Area LIP: Guiding eye movements -Delayed-saccade task – Like ‘QV’ cells in S. C. - activity ‘holds’ motor error info Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Concluding Remarks • Learning and memory – Occur throughout the brain • Memories – Duration, kind of information stored, and brain structures involved – Distinct types of memory – Different types of amnesia • Multiple brain systems for memory storage • Engrams in temporal lobe neocortex – Physiological basis? – Long-term memories: structural basis? Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

End of Presentation Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Types of Memory and Amnesia • Amnesia: Serious loss of memory and/or ability to learn • Causes: Concussion, chronic alcoholism, encephalitis, brain tumor, stroke – Limited amnesia (common) – Dissociated amnesia: No other cognitive deficit (rare) Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

Types of Memory and Amnesia • Amnesia (Cont’d) – Transient global amnesia: Shorter period, temporary ischemia (e. g. , severe blow to head) – Symptoms: Disoriented, ask same questions repeatedly; Attacks subside in couple of hours; Permanent memory gap Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Search for the Engram • Localization of Declarative Memories in the Neocortex – Human extrastriate cortex differentially activated in car and bird experts Copyright © 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins