Lecture 6: Memory & Amnesia (PYB102)

Lecture 6 ========= PYB102 AUG 29, 24 One way of conceptualising memory\... BP5e-Fig-17-13-0 Memory by time - The multiple- trace hypothesis of memory classifies memory by duration: I. Iconic memories are the briefest II. Short term memories (STMs) are longer III. The most enduring fr...

Lecture 6 ========= PYB102 AUG 29, 24 One way of conceptualising memory\... BP5e-Fig-17-13-0 Memory by time - The multiple- trace hypothesis of memory classifies memory by duration: I. Iconic memories are the briefest II. Short term memories (STMs) are longer III. The most enduring from of memory is long- term memories (LTMs) which can last for days or years. Another way of conceptualising memory  Memory by type (1) - Nondeclarative (procedural) memory: Things you know that you can show by doing (e.g., grammar, or motor skills, or problem- solving) - Declarative memory: Things you know that you can tell other (e.g., facts and events) - Two subtypes of declarative memory: I. Semantic memory: generalised memory II. Episodic memory: autobiographical Memory by type (1) - Nondeclarative or procedural memory is shown by performance rather than by conscious recollection. - This memory without conscious awareness is sometimes referred to as 'implicit' memory. It is often contrasted with 'explicit' memory (conscious memory). BP5e-Fig-17-05-0 Brain structures involved in learning and memory - Our knowledge of the brain structures involved in learning and memory has to a large extent come from the study of neuropsychological patients with brain damage-produced amnesia. - It is important to review some of these critical case studies and their implications for our understanding of the neuroanatomical bases of memory. Henry Gustav Molaison (H.M.) - Born February 26^th^, 1926, died December 2^nd^, 2008 - Seizures began at age 10 - From age 16-27, had \~10 partial seizures a day, 1 generalized seizure a week - Seizures not controlled by antiepileptic medications - EEG showed abnormalities in central temporal lobes - At age 27, a bilateral medial temporal lobectomy was performed on H.M. - This involved the removal of the medial portions of both temporal lobes including most of the hippocampus, amygdala and adjacent cortex (rhinal cortex). - Following the surgery: - Preserved perceptual and motor abilities - Preserved STM - Some retrograde amnesia - Severe anterograde amnesia Which kind of amnesia was that? (I forget....) - Anterograde amnesia = loss of memory ***after*** injury event - Retrograde amnesia = loss of memory ***prior*** to injury event  Formal assessment of HM's amnesia - Digit span + 1 test - Block tapping memory span test - Mirror drawing test - Incomplete pictures test BP5e-Fig-17-02-0  Formal assessment of HM's amnesia - Digit span + 1 test - Showed HM's inability to form new long-term memories for verbal information - Block tapping memory span test - Showed that his inability to form new memories was not just restricted to verbal information - Mirror drawing test - Despite not remembering the test, HM's performance improved - Incomplete pictures test - Despite not remembering the test, HM's performance improved figure\_08\_22  Case studies are all very well but... - The first reports of HM's case in the 1950's triggered a massive effort to develop an animal model of his disorder so that it could be subjected to experimental analysis. - In its early years, this effort was a dismal failure; lesions of medial temporal lobe structures did not produce severe anterograde amnesia in rats, monkeys, or other nonhuman species. The delayed non-matching-to-sample task. - An important advance was the development of a method for testing declarative memory in monkeys- the delayed non-matching-to-sample task. - The development of this task for monkeys also provided a means of testing the assumption that the amnesia resulting from medial temporal lobe damage is entirely the consequence of hippocampal damage. bp5e-fig-17-09-0  ch11fig11 What do these studies tell us? - Reviewers of this research have generally reached these conclusions - Bilateral surgical removal of the perirhinal cortex consistently produces severe and permanent deficits in performance on the delayed non-matching-to-sample test and other tests of object recognition. - In contrast, bilateral surgical removal of the hippocampus produces either moderate deficits or none at all, and; - Bilateral destruction of the amygdala has no effect on object recognition. So what about the hippocampus? - Memory Formation and Consolidation: The hippocampus still plays a role in forming new memories and reorganising them over time - Temporary Storage: It plays a temporary role in memory storage, with damage typically impairing recent but not remote memories - Spatial Representation: The hippocampus is involved in representing spatial information and navigation. - Memory Retrieval: It works with the cortex to support long-term memory storage, with its role gradually declining as memories become more stable in the cortex. Synaptic mechanisms of learning and memory - There are many hypotheses as to the neural mechanisms of learning and memory. - These tend to centre on: - Structural changes at synapses - Physiological changes at synapses - Structural changes at synapses may include: - Formation of new synapses - Rearrangement of synapses - Neurogenesis  - Physiological changes at synapses may include: - Long-term potentiation (LTP) - a stable and enduring increase in the effectiveness of synapses Long-term potentiation (LTP) - *Repeated firing of a synapse lowers the threshold for that synapse to fire* - Time 1 (before any change happens) pre-synaptic neuron fires at a normal rate - post-synaptic neuron fires at a certain strength in response LTP -- Stage 2 (induction) - Time 2 (the cause of the change) - pre-synaptic neuron fires a lot, causing post-synaptic neuron to fire a lot  LTP -- Stage 3 (expression) - Time 3 (after the change) - presynaptic neuron fires at a normal rate - post-synaptic neuron now fires more strongly than it did at Time 1 Mechanisms of LTP (i) - LTP has been studied most extensively at synapses at which the NMDA receptor is prominent. - The NMDA receptor is a receptor for glutamate- the main excitatory neurotransmitter of the brain. - An NMDA receptor has a special property- it does not respond maximally unless two events occur simultaneously: - Glutamate must bind to it, and; - The postsynaptic neuron must already be partially depolarised. Mechanisms of LTP (ii) - This dual requirement stems from the fact that the calcium channels that are associated with NMDA receptors allow only small numbers of calcium ions to enter unless the neuron is already depolarised when glutamate binds to the receptors; it is the influx of calcium ions that triggers action potentials and the cascade of events in the post-synaptic neuron that induces LTP.  bp5e-fig-18-09-2r