A. HM, B. Spa@Al Naviga@On 2. Hippocampus

Outline

1. What does Hippocampus do? A. HM, B. Spaal navigaon 2. Hippocampus anatomy and connecvity CA1, CA3 diagram etc. Connecvity to other regions. 3. Place fields in Hippocampus – show examples + the O'Keefe effect 4. Plascity of place fields + NMDA blocker + Morris water maze 5. Replay of sequences 6. Entorhinal grid cells What does the Hippocampus do?

1. Memory

2. Spaal representaon Henry Gustav Molaison (February 26, 1926 – December 2, 2008), beer known as HM

“Aer operaon this young man could no longer recognize the hospital staff nor find his way to the bathroom, and he seemed to recall nothing of the day-to-day events of his hospital life. There was also a paral retrograde amnesia, inasmuch as he did not remember the death of a favorite uncle three years previously, nor anything of the period in the hospital, yet could recall some trivial events that had occurred just before his admission to the hospital. His early memories were apparently vivid and intact. This paent’s memory defect has persisted without improvement to the present me, and numerous illustraons of its severity could be given. Ten months ago the family moved from their old house to a new one a few blocks away on the same street; he sll has not learned the new address, though remembering the old one perfectly, nor can he be trusted to find his way home alone.” “Moreover, he does not know where objects in connual use are kept; for example, his mother sll has to tell him where to find the lawn mower, even though he may have been using it only the day before. She also states that he will do the same jigsaw puzzles day aer day without showing any pracce effect and that he will read the same magazines over and over again without finding their contents familiar. This paent has even eaten luncheon in front of one of us (B.M.) without being able to name, a mere half-hour later, a single item of food he had eaten; in fact, he could not remember having eaten luncheon at all. Yet to a casual observer this man seems like a relavely normal individual, since his understanding and reasoning are undiminished.”

W. B. Scoville & B. Milner, Loss of recent memory aer bilateral hippocampus lesions. J. Neurol. Neurosurg. Psychiat., 20: 11-21, 1957.

Note – this is a deficit in declarave memory

Morris water maze

Morris et al 1982 Some Anatomy

From Rosene & Van Hoesen (1987)

From Amaral & Witter (1989) Neuroscience 31: 571-591

“The hippocampus is the core of a neural memory system providing an objective spatial framework within which the items and events of an organism’s experience are located and interrelated.” J. O’Keefe & L. Nadel (1978) The Hippocampus as a Cognitive Map Oxford University Press, p. 1. The Hippocampal Circuit

SC – Schaffer collateral mf – Mossy fiber Actually goes to DG – Dentate gyrus DG, CA1 and CA3 pp – perforant path

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From N. M. van Strien, N. L. M. Cappaert & M. P. Wier, review (2009)

Auditory, Visual olfactory cortex corces Connecvity with

Posterio different Brain areas Entorhinal Hippocampus r parietal cortex cortex

Retrosplenial cortex

Anterior Subiculum Post- dorsal subiculum nucleus

Lateral Lateral Medial dorsal mammillary mammillary nucleus nuclei nuclei

Dorsal Ventral tegmentum tegmentum

Medial Striatum vesbular via motor nuclei cortex Observaon: CA1 is a feed forward structure, there are very lile recurrent connecons within CA1.

CA3 in contrast has many recurrent connecons.

Dentate gyrus – very high dimensionality.

Ideas: CA3 – recurrent (aractor) network – paern compleon.

Dentate gyrus – paern separaon.

These ideas are oen associated with Marr and Albus.

There is something quite vague about the use of these ideas in Neuroscience.

The tetrode

From Amaral & Witter (1989) Hippocampal Place Cells

From Wilson and McNaughton, but place cells first found by O’Keefe and Dostrovsky (1971) hippocampal coding video

Video from: Kemere, Karlsson and Frank Place cells / Place fields

Wilson & McNaughton Long-term stability of place fields

From Thompson & Best (1990) Brain Res. 509: 299-308. Remapping of place cells in a new environment

Lever et al (2002) Remapping with change of boundary walls

Lever et al (2002) Over me the place fields in the different environments diverge Place field properes depend of NMDAR Navigaon depends on NMDAR

Morris 1989 Phase precession

Huxter, Burgess, Okeefe, 2003

Reverse Replay (Foster and Wilson 2006)

Place field and predicon in T maze

Wood et al, Neuron 2000 Grid cells in Entorhinal cortex

Dorsal most (towards the back in neurospeak)

Ventral most (front in neurospeak) Step like increase in grid cell spacing Discrete Set of grid orientaons Summary