Describe the anatomy of the limbic system. How does it contribute to memory?

Sanjay Manohar, Oxford 2017

Intro

Maclean - 1950s limbic system reptiles
Broca 1878 le grand lobe limbique

"regulated response to environment, with respect to internal state."

Emotion

 olf cx -> septal accumbens hypothal -> stria terminalis
 assoc cx -> BL -> centromedian -> autonomic endocrine (ventral amygdalofugal)
 centromedian = visceral; 
 VS/VP/OFC pathway receives input from here.
 merges into periamygdaloid cortex (surface of uncus)
 inputs: olfactory, visceral, orbital and insular 
 entorhinal, HC, MD thal -> amyg -> consolidation of emotional memories
  
 lesions disrupt fear face processing
 fmri -> fear faces
 Murray 2006 - associative fear learning disrupted in rats
 Paton 2006 - record amygdala - associative value of stimuli.
 
2011 Feinstein Urbach Weithe syndrome - bilat amygd - empathise fear but do not feel it; but still get panic for high CO2.

2010 Labuschagne - Generalised anxiety disorder -> amyg hyperactivity. Oxcytocin intranasal normalises this. 

Rolls 2003 - amyg discriminates odors on fMRI. Lateral unpleasant, medial pleasant.
1939 Kluver Bucy: visual agnosia, hyperoral, hypermetamorphosis, placidity, sexual. 

2011 Lin optogenetic vm hypothal: stim-> anger. silencing ->placid.

2010 Adhikari elevated plus maze - anxiety. mPFC + vHC firing correlate with anxiogenic movts. sync with mFC

Motivation

 - 1994 Salamone accumbens distress calls, facial expression
 - hypothalamus. 
 
Autonomic function
 -SON subfornicl organ preoptic n, ant hypothal. 

Memory

 - HC neurogenesis Altman 1965
 - Papez
 - Tulving 1972 - knowing vs remembering = semantic / episodic. autobiographical. flashbulb memory. 
 - Mishkin 1978 - primate MTL lesions (hipp+amyg) DNMTS-unique impaired (but not after WM lesions). 
 - Zola morgan and squire 1982 - specifically hippocampal lesions = memory, amyg = emotional. much more sever if bilat. Perirhinal+parahipp lesions = severe memory loss too.
 - CA1 v sensitive to ischaemia.  
 - Time, Place, Grid, Border cells, head direction, path integration.
 - binding (Squire 1989)
 - Nadel 1997 - HC lesions impair consolidation not immediate memory. -> retrograde
 
 - EC -> (perforant path) -> DG ->(mossy) -> CA3 ->(schaffer) -> CA1 -> subiculum
   CA1+Subic -> alveus - fimbria -crus fornix
   subiculum transitions to 6-layered cx
   fx: -> hippocampal commissure, septal, preoptic, striatum, ofc, acc, ant   thal, mammillary, hypothalamus, midbrain rf 
   
 - 1973 Bliss and Lomo: tetanic stim facilitates.
   NMDA hypothesis of LTP.
   Ca++ -> phosphorylation and exocytosis of AMPAR
   
 - Dudek and Bear 1992 - LTD with nonsynchronous stim
   endocytosis of AMPA. Kandel 2008: blocking LTD (NMDA) causes perseveration on water maze.
   
 nonassociative mossy-CA3 - calcium potentiates glu release. 
 associative schaffer-CA1 - NMDA-dependent.
 limbic encephalitis - VGKCA, NMDA; Herpesviruses predilection
   - now treatable!

 
 - calcium chelators block LTP
 - Sanheuza - LTP reversed by CN peptides
 - effects: upregulate receptors, CaMKII, synaptotagmin, morphological.
 - Emptage 2003 - LTP from increased presynaptic release
 - Enoki 2009: stim schaffer collaterals, EPSP unchanged --> increased presynaptic probability of release, not postsynaptic sensitivity. 
   recruitement of more presynaptic release sites?
 - early vs late LTP - PKMzeta (PKC) blockade impairs late LTP.
 
 - STDP Levy & Steward 1983; Bi and Poo 1998
  
  Schizophrenia - NMDA hypofunction? MHC-1 might be relevant
  fragile X: regulates mGluR translation. enhanced LTD.
 2016 Puzzo extracellular tau HC:  impaired LTP, alters fear conditioning, but not cued fear.
  1957 scoville and milner - HM epilepsy - spatial episodic declarative, intact procedural and priming.
  VGKCA / NMDA receptor antibody syndrome
  Ribot's law - consolidation -> amnesia is graded.
  2000 Maguire vbm taxi drivers.
 - O'keefe and dostrovsky 1971 - place cells
   (cf Tolman 1948)
 - Tsien 1996: NMDAA knockout HC impairs spatial not nonspatial memory.
 - 2005 Hafting Moser Moser - characterised grid cells EC. "infinite size map". topographic : spacing orientation and size.
  - Solstad 2008 - boundary cells in MEC.
  2011 Macdonald: CA1 sequential activity indicating "time" in trial. Some Scale with delay -> relative time vs absolute time. 
  Korsakoff B1,  mammillo/DMthal
  - Treyer 2003 - source memory left OFC + VS + caudate, WN, medial thal.
  - Lavilleon 2015 sleep stim mfbb - mice showed place preference on waking. 
  
 - Morris 1984: water maze. submerged platform. disrupted by NMDA blockade.
 
 

Conclusion

 Nonmnemonic hippocampal functions
 - Pattern separation and completion (Marr 1971)
 - role in working memory (binding)
 - Temporal lobe epilepsy - deja vu, jamais vu, dissociative, derealisation