PSYC 271 Chapter 11
Korsakoff's syndrome
Due to thiamine deficiency ◦ Amnesia (severe anterograde and retrograde) ◦ Confusion ◦ Personality changes
Case of H.M.
- Suffered from severe epilepsy - He had a bilateral medial temporal lobectomy which removed: ◦ Hippocampus ◦ Amygdala ◦ Entorhinal cortex ◦ Perirhinal cortex - H.M. suffered from devastating amnesia as a result of his operation - H.M. can demonstrate his retention of certain types of tasks by his improved performance on them, although he has no conscious recollection of previously practicing them
How memories are consolidated
- The hippocampus sends information to different cortical areas during memory encoding - During encoding these areas are all active at the same time, and this pattern of activation is imprinted - Hippocampal activation of multiple cortical areas strengthens the connections between these areas - Connections between cortical areas is now strong and no longer requires hippocampal activity. HOWEVER each time a memory is retrieved from long term memory it is temporarily held in short term memory and is susceptible to interference.
Evidence of Hippocampus Role in Spatial Memory
1. Animals with hippocampal lesions ◦ Poor performance on the Morris water maze (spatial memory) ◦ Poor performance in the radial arm maze (reference and working memory) 2. Hippocampal place cells; these cells fire when a rat is placed in a specific location (in the place field), but only after the rat becomes familiar with that location. 3. Comparative research has revealed that the hippocampus plays a role in the spatial memory of many different species. · For example, Sherry and his colleagues (1989) have reported that food-caching birds tend to have larger hippocampi than noncaching species.
Neuroanatomical Basis for Object Recognition Deficits
1. Bilateral hippocampal lesions that do not damage the overlying cortex produce only mild deficits in DNMTS tests 2. Bilateral lesions of the amygdala produce no deficits 3. Bilateral lesions to the rhinal cortex produce major deficits
Types of long term memory
1. Implicit 2. Explicit
Delayed non-matching to sample task steps
1. Monkey moves sample object to obtain food from underneath it 2. Screen is lowered during the delay period 3. Monkey is confronted with sample object and an unfamiliar object 4. Monkey must remember the sample object and then select the unfamiliar object to obtain the food underneath it
Types of memory
1. Short term 2. Long term 3. Working memory
Major contributions to H.M.'s case
1. The hippocampus and surrounding structures are essential for memory 2. Hippocampus is involved in creating and consolidating explicit memories, but not involved in short term memory or remote memory retrieval. 3. Explicit and implicit memories are formed and recalled via different processes.
Amnesia
A deficit in memory that is due to damage, disease, or psychological trauma.
Delayed non-matching to sample task
An object recognition task in which the correct target object during the test does not match the cue object
Hippocampus and Spatial Memory
Animals with hippocampal lesions ◦ Poor performance on the Morris water maze (spatial memory) ◦ Poor performance in the radial arm maze (reference and working memory)
Grid Cells
Cells within the entorhinal cortex that have extensive arrays of evenly spaced place fields.
Explicit memory
Declarative memories, facts, locations; branches into facts (semantic) and events (episodic)
Border cells
Fire when the subject is near the borders of an environment
Working memory
For short term processing and manipulation of information for complex tasks (i.e. comprehension, learning, and reasoning).
Synaptic mechanisms of learning and memory
Hebb (1949) ◦ Changes in synaptic efficiency are the basis of long term memory formation and storage. ◦ Greater efficiency between synapses occurs when the synaptic connections between neurons become stronger. ◦ Synapses are effectively made stronger by repeated stimulation. ◦ Key Concept: Co-occurrence of firing in pre- and postsynaptic neurons necessary for learning and memory
What cells within the MTL are the most particular?
Hippocampal cells
Memory
How changes are created, stored, and later reactivated.
Induction of LTP
Induction of LTP requires a molecular change within the post synaptic neuron in order to produce a long term change in its behavior. This molecular change has been most often studied in neurons that contain NMDA receptors.
Cerebral Ischemia (Case of R.B.)
Insufficient blood flow to the brain; R.B. suffered damage to just one part of the hippocampus (CA1 pyramidal cell layer) and developed amnesia as a result of a cerebral ischemia. R.B. suffered amnesic deficits similar too but less severe than H/M. Suggests that hippocampal damage alone can produce amnesia.
Long term potentiation (LTP)
Long term (up to several weeks) increase in the synaptic strength of neurons as a result of intense high frequency stimulation.
Hebb's Theory of Memory Consolidation
Memories are stored in the short term by neural activity. Interference with this activity prevents memory consolidation.
Long term memory
Memories maintained in long term storage for future use.
Delayed non-matching to sample task results
Monkeys with bilateral MTL lobectomies demonstrate differential deficits in memory, depending on the length of the delay. Short Delay (seconds) - No major deficit. Long Delay (several minutes) - Major object recognition deficits. Monkeys with MTL damage very susceptible to distraction.
Short term memory
Our moment to moment conscious thoughts and perceptions.
Hippocampal Place Cells
Respond when the rat is in a specific place field, but only after the rat becomes familiar with the location.
NMDA Receptors
Special type of glutamate receptor that only allows the passage of ions when the neuron on which they are situated is already partially depolarized. Interestingly, NMDA-mediated activation of postsynaptic neurons requires that the postsynaptic cell already be depolarized by concurrent activation by non-NMDA receptors; this requirement for co-occurrence of activity provides further support for Hebb's postulate and the putative role of LTP in learning. - Full activation of NMDA receptors allows Ca2+ ions to enter postsynaptic neurons; this Ca2+ influx is believed to activate protein kinases that are responsible for the induction of LTP. Short term changes as a result of NMDA activity are increased migration of AMPA receptors to the postsynaptic membrane. This increases the cells likelihood of firing in response to presynaptic activity. Key Concept: NMDA receptors signal simultaneous converging activity at the post synaptic neuron. AMPA are the brains primary glutamatergic ionotropic receptor. - Opens in response to glutamate to allow Na+ to enter the cell causing local depolarization. - If there is enough local depolarization, NMDA receptors will lose their Mg+ block becoming active. - Activation of these receptors allows Ca+ to enter the cell, activating second messenger systems - The most immediate change is increased migration of AMPA receptors to the post synaptic membrane. Key Concept - Because the NMDA receptor requires the neuron to already be partially depolarized in order for it to respond to glutamate release at the synapse -> there must be simultaneous activity in at least two converging inputs to the post synaptic neuron. - This mechanism therefore allows for associations to be made between stimulus inputs at a synaptic level.
Transient Global Amnesia
Sudden onset severe anterograde amnesia lasting 4 - 6 hours as a result of CA1 damage.
Learning
The process by which experience changes the brain.
Gradients of Retrograde Amnesia and Memory Consolidation
The retrograde amnesia seen after concussion or coma is typically worse for the most recent memories; this led to the suggestion that older memories are stored in a more permanent form through the process of consolidation. Note: Long gradients of retrograde amnesia are inconsistent with consolidation theory.
Head-direction cells
Tuned to the direction of head orientation
Implicit memory
Unconscious memory; branches into priming, procedural, associative learning (classic and operant condition) and non-association learning (sensitization, habituation)
Maintenance and expression of LTP
Unlike induction, maintenance and expression of LTP require both pre- and postsynaptic changes. Long term maintenance and expression rely on protein synthesis that change the; ◦ Number and size of synapses ◦ Density of dendritic spines ◦ Post synaptic receptor expression ·LTP develops only at specific presynaptic inputs (that are active during periods of postsynaptic depolarization), due to postsynaptic dendritic spines that restrict the movement of Ca2+ in the postsynaptic neuron to only those synapses that are activated by high-frequency stimulation. · LTP activates numerous transcription factors that are responsible for the structural changes that accompany LTP. Researchers have documented increases in the number and size of synapses, dendritic spines, and in the number of postsynaptic receptors that exist following the induction of LTP. In order for both pre-and postsynaptic changes to occur in the late phases on LTP the postsynaptic neuron must signal the presynaptic one. Nitric Oxide (NO) ◦ Soluble gas neurotransmitter synthesized in the post synaptic cell in response to Ca+ influx ◦ Diffuses across the synapse to the presynaptic neuron ◦ Increases release of presynaptic neurotransmitters · Nitric oxide (NO), a soluble gas neurotransmitter that is produced by postsynaptic neurons during periods of activation, serves as the signal that passes from the postsynaptic neuron back to the presynaptic neuron to induce the changes that underlie the maintenance of LTP. Most LTP research has focused on NMDA-receptor-mediated LTP in the hippocampus. BUT LTP is mediated by different mechanisms in other areas of the brain. LTD (long-term depression) also exists. Much of LTP and the neural basis of memory is still a mystery, despite many research discoveries.
Repetition Priming Test
Used to assess implicit memory; - patients are shown a list of words and some time later they are shown a series of word fragments and asked to complete the words. - Amnesic patients do as well on this task as control subjects, even though they do not remember ever seeing the original list of words.
Digit Span +1 Test
◦ 5 digits presented at 1 second intervals ◦ Correct recall adds 1 digit ◦ 6 digits presented until correctly recalled, then 1 digit added ◦ Etc. H.M. Could only get to 7 digits (1 more than his digit span)
Pavlovian Conditioning Test
◦ Cue is paired with a puff of air to the eye ◦ Unconditioned blinking response becomes conditioned ◦ Blink response to cue alone ◦ H.M. retained the conditioned response despite having no conscious awareness of the conditioning.
Memory tasks
◦ Digit Span +1 Test ◦ Block Tapping Memory Span Test ◦ Mirror Drawing Test ◦ Incomplete Pictures Test ◦ Pavlovian Conditioning
Complex role of Hippocampus
◦ Hippocampal damage has differential effects on episodic memory impairment (recall vs recognition) ◦ Spatial memory is thought to rely on place cells, but place cell activity sometimes depends on other behaviors. ◦ Hippocampal damage sometimes impairs behavior without a spatial component. ◦ The hippocampus is large and complex, and its component substructures need to be evaluated in more detail.
Storage
◦ Hippocampus = spatial location ◦ Perirhinal cortex = object recognition ◦ Inferotemporal Cortex = visual memories ◦ Amygdala = Memories with emotional significance ◦ Prefrontal Cortex = memory of temporal order of events and working memory ◦ Cerebellum and Striatum = habits, conditioned motor responses, implicit sensorimotor learning.
The Standard Consolidation Theory
◦ Hippocampus holds memories until they can be transferred to long term storage in the cortex.
Incomplete Picture Test
◦ Incomplete images are presented ◦ An images not correctly identified are then presented in their "more complete" form. ◦ Continues until complete images are presented.
Memory as a function of LTP can be viewed as a three-part process.
◦ Induction (learning) ◦ Maintenance (memory) ◦ Expression (recall)
Block Tapping Memory Test
◦ Series of blocks laid out (physically or digitally) ◦ Blocks are tapped randomly at 1 second intervals ◦ Correct recall adds another block ◦ H.M. Could only recall sequences of 5 blocks.
Alzheimers
◦ Short term memory and implicit memory deficits ◦ Major anterograde and retrograde amnesia in explicit memory tests ◦ Widespread damage observed in the basal forebrain, medial temporal lobes, and prefrontal cortex - Enlargement of the ventricles - Severe shrinkage of the hippocampus - Atrophy of the cortex
Case of N.A and Korsakoff's syndrome
◦ Stabbed in the brain with a fencing foil ◦ Damage to the cribriform plate, mediodorsal thalamic nuclei, and mammillary bodies (can occur without damage to MB). ◦ Suffered retrograde and anterograde amnesia.
Mirror Drawing Test
◦ Trace a shape using feedback from a mirror ◦ Tracing hand is obscured from view ◦ H.M. displayed substantial learning without having any conscious recall of performing the task previously.
