Neuroscience: Exploring the Brain, 3e http://www.pbs.org/saf/1402/video/watchonline.htm Neuroscience: Exploring the Brain, 3e Chapter 24: Memory Systems http://www.pigeon.psy.tufts.edu/asc/Mizumori/Default.htm

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

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

Types of Memory and Amnesia Long-Term, Short-Term, and Working Memory Working memory: Temporary information storage requiring rehearsal Sensory information Short-term memory Consolidation Long-term memory Short-term memory Sensory information Consolidation Long-term memory Time

Types of Memory and Amnesia Retrograde amnesia: Forget things you already knew Anterograde amnesia: Inability to form new memories

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

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

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

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?

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.)

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

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

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/SoxsMMV538U

http://youtu.be/SoxsMMV538U http://youtu.be/SoxsMMV538U Memory capacity: Jill Price http://youtu.be/SoxsMMV538U http://youtu.be/SoxsMMV538U

The Temporal Lobes and Declarative Memory The Medial Temporal Lobes and Declarative Memory Information flow through medial temporal lobe

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

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

The Temporal Lobes and Declarative Memory The Diencephalon and Memory Processing Brain regions associated with memory and amnesia outside the temporal lobe

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

The Temporal Lobes and Declarative Memory Memory Functions of the Hippocampus Hippocampal responses to old (familiar) and new stimuli

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).

The Temporal Lobes and Declarative Memory http://www.pigeon.psy.tufts.edu/asc/Mizumori/Default.htm The Temporal Lobes and Declarative Memory http://youtu.be/PGHRDcPKio8 http://youtu.be/lfNVv0A8QvI 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

Place cells Grid Cells

Place field: http://youtu.be/PGHRDcPKio8

Place cell activity http://www. youtube. com/watch

The Temporal Lobes and Declarative Memory http://www.pigeon.psy.tufts.edu/asc/Mizumori/Default.htm The Temporal Lobes and Declarative Memory http://youtu.be/PGHRDcPKio8 http://youtu.be/lfNVv0A8QvI 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

Causal role of hippocampal cell activity in establishing associative memories c-fos-tTA transgenic mice: promoter of the c-fos gene drives the expression of the tetracycline transactivator (tTA) to induce expression of a gene downstream of the tetracycline-responsive element (TRE) (8–12). Inject AAV4 virus encoding TRE-ChR2-mCherry into the DG or CA1 of c-fos-tTA animals

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

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.

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

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

The Neocortex and Working Memory

The Neocortex and Working Memory The Prefrontal Cortex and Working Memory Working memory activity in monkey prefrontal cortex

The Neocortex and Working Memory The Prefrontal Cortex and Working Memory Wisconsin card-sorting task

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

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

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?

End of Presentation

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)

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

The Search for the Engram Localization of Declarative Memories in the Neocortex Human extrastriate cortex differentially activated in car and bird experts