Cellular Neurobiology BIPN140

Second midterm is next Tuesday!! Covers lectures 7-12 (Synaptic transmission, NT & receptors, intracellular signaling & synaptic plasticity).

Review session is on Monday (Nov 14th) before midterm 6:00-8:00 PM at 3500 Pacific Hall (Code: 286856). Please come with questions.

Peixin’s section tomorrow (2:00-3:00) is cancelled due to Veteran's Day. Additional office hour will be held by Milad & Antonia tomorrow at Pacific Hall 3502, 12:00-2:00 PM.

PS 6 Q&A is now posted on the website 2015 Problem sets #4~ #6 and 2nd midterm are also posted!

Chih-Ying’s Office Hour: Monday, 1:00-2:00 PM, Bonner Hall 4146

BIPN140 Lecture 14: Learning & Memory

1. Categories of Memory 2. Anterograde v.s. Retrograde Amnesia 3. Brain regions critical for memory

Su (FA16) The Major Qualitative Categories of Human Memory (Fig. 31.1)

episodic semantic classical conditioning Priming: a change in the processing of a stimulus due to a previous encounter with the same or similar stimulus

Temporal Categories of Memory: Phases of Memory (Fig. 31.2) Patient H.M. & Brenda Milner (Box 31c)

(Brenda Milner, 1918-) (H.M. 1926-2008)

http://www.pbs.org/wgbh/nova/body/corkin-hm-memory.html

H.M.: Learning without Realizing it

(Kandel et al., Principles of Neural Science, 5th Edition) Brain Areas Associated with Declarative Memory Disorders (Fig. 31.9a)

Amygdala: required for fear-based memory

Spatial Learning & Memory in Rodents Depends on the Hippocampus (Fig. 31.10) The Case of London Taxi Drivers (Fig. 31.12A)

Spatial hypothesis of hippocampal function: the “spatial maps” stored in the hippocampus enable flexible navigation by encoding several routes to the same direction.

(n=16)

(Eleanor Maguire et al., PNAS 97:4398-4403, 2000)

The Case of E.P.

Spatial hypothesis of hippocampal function: the spatial maps stored in the hippocampus enable flexible navigation by encoding several routes to the same direction. Is it so for humans?? Is hippocampus critical for the “retrieval” of spatial memory?

Topographical Memory Test

(Teng & Squire, Nature 400: 675-677, 1999) The Case of E.P.

Larry Squire’s Patient EP (https://www.youtube.com/watch?v=3XHfJiSmEy8)

Classical Conditioning (Associative Learning)

(Kandel et al., Principles of Neural Science, 5th Edition) Memory Engram (Fig. 31.3)

The Acquisition and Storage of Declarative vs Non- declarative Information (Fig. 31.17) (Kandel et al., Principles of Neural Science, 5th Edition)

Memory and Aging (Fig. 31.18 & 31.19)

Mentally active, high-performing older adults may offset declines in processing efficacy. Eric Kandel is 86; Brenda Milner is 97  Background: Ablation or disruption of hippocampal neurons impairs memory, suggesting that hippocampus is necessary for memory formation. However, it is unclear whether activation of a specific population of hippocampal neurons that were activated during learning is sufficient to elicit the behavioral output of a specific memory. Is there specific memory engram in the hippocampus?

 Experiments: Use a genetic approach + viral injection to selectively express ChR2 in hippocampal neurons that are activated during learning. Later on, use blue light to activate ChR2 expressed in those neurons and see whether animals behave as if they recall a fear memory (freezing).

 Results: Optogenetic activation of those hippocampal neurons is sufficient to induce fear memory. In addition, light-induced fear memory recall is context- specific, that is, activation of cells labeled in a different context does not induce fear memory. Therefore, activation of a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Fig. 1. Selective labeling of dentate gyrus cells by ChR2-EYFP

 Dentate gyrus (DG): critical in discriminating between similar contexts of fear memory.

 About 2-4% of the neurons are activated (immediate early gene expression) in a given context.

 DG is an ideal target for the formation of contextual memory engrams that represent discrete environments.

DG CA1 CA3 ChR2-EYFP c-fos-shEGFP c-fos-shEGFP

c-fos promoter + tTA (tetracycline trans-activator) => suppressed by doxycycline Tetracycline responsive element (TRE) site + ChR2-EYFP

Fig. 2. Activity-dependent expression and stimulation of ChR2-EYFP

Dox (-) Dox (-) Dox FC

(-) Dox 5 days 30 days NS

seizure c-fos positive staining after blue light stimulation Exp: TRE-ChR2-EYFP Ctrl: TRE-EYFP Fig. 3. Optical stimulation of engram-bearing cells induces post-training freezing

Light-induced memory recall No shock, just CS No ChR2, negative control

CS induced freezing: ~60%

Bilateral injection

Direct activation of a subset of neurons involved in the formation of a memory is sufficient to induce the behavioral expression of that memory!!

Fig. 4. Labeling and stimulation of independent DG cell populations (context specific)

Open field

ChR2-EYFP c-fos (context C) (context B)

Two separate populations of DG neurons are recruited to represent two different contexts