O'Keefe Lab

Honeycomb maze raised platform
Research Area

The hippocampus and amygdala, both members of the limbic system in the temporal lobes, provide two distinct types of memory. The hippocampal formation underpins spatial memory, providing long-term memories for locations and a neural mechanism for supporting navigation and exploration. In contrast amygdala provides short-term memories for ecologically significant information such as an interaction with a particular conspecific or the consumption of a particular food.

Our current research is directed toward unravelling the role of the entorhinal cortex and hippocampus in spatial memory and understanding the mechanisms underlying short-term memories in the amygdala.  

Research Topics

We employ a range of technologies including tetrode and high density neuropixels electrophysiological probes, two photon imaging in conjunction with virtual reality environment, and novel maze tasks to study the spatial correlates of hippocampal and medial entorhinal cortical cells. Figure 1 shows the fields of 12 entorhinal grid cells recorded 47 days after implantation of a neuropixels probe. 

Waveforms of medial entorhinal cortical cells

Figure 1. Waveforms of 12 (of 22) medial entorhinal cortical cells (C) from a total of 127 cells (B) recorded with a neuropixels probe (A). Bauza (unpublished)

In recent work we have shown that the grid structure is not uniform across the whole of a nonhomogeneous environment such as a trapezoid and that single fields can be manipulated by the movement of nearby walls of the enclosure. Figure 2 shows that the symmetrical grid pattern recorded from a grid cell in a square is distorted and much less gridlike in the trapezoid. This finding calls into question how useful the grid system is for providing a metric for the cognitive map and suggests that the grids are more responsive to the shape of the enclosure than had previously been suspected. 

Grid cells in strong and weak patterns

Figure 2. Grid cell with a strong grid pattern in a square enclosure has a much weaker grid pattern in trapezoid where the grid is bent and stretched on the left-hand side. Krupic et al 2015

Cells in the amygdala respond selectively to stimuli of ethological significance such as a conspecific or a specific food, and continue to fire after the removal of that stimulus for periods of minutes. We are trying to understand the mechanism underlying this short-term response and to understand its function. Does it provide a memory of the event or does it provide some other type of signal for example enabling other areas of the brain to consolidate information stored at the time of an important ethological event. 

John O'Keefe
Professor of Cognitive Neuroscience
Marius Bauza
Senior Research Fellow
Joseph Catling
Research Technician
Eylon Dary
PhD Student
Carla Griffiths
Research Fellow
Loukia Katsouri
Senior Research Fellow
Filipa Lourenco de Almeida
PhD Student, Institute of Neurology
Chenyue Ren
Research Technician
Laura Schwarz
PhD Student
Stephen Burton
Experimental Officer
Cristina Mazuski
Research Fellow
Lennart Oettl
Research Fellow
Jake Ormond
Senior Research Fellow
Selected publications

Hippocampal place cells have goal-oriented vector fields during navigation

Ormond J, O'Keefe J
Published by:
Nature (607: 741-746) (doi: 10.1038/s41586-022-04913-9)
06 July 2022

Representation of ethological events by basolateral amygdala neurons

Mazuski C, O'Keefe J
Published by:
Cell Reports (39: 110921) (doi: 10.1016/j.celrep.2022.110921)
07 June 2022

Two Distinct Types of Eye-Head Coupling in Freely Moving Mice

Meyer AF, O'Keefe J, Poort J
Published by:
Current Biology (30: 2116-2130) (doi: 10.1016/j.cub.2020.04.042)
14 May 2020

Local transformations of the hippocampal cognitive map

Krupic J, Bauza M, Burton S, O'Keefe J
Published by:
Science (359: 1143-1146) (doi: 10.1126/science.aao4960)
09 March 2018

The honeycomb maze provides a novel test to study hippocampal-dependent spatial navigation

Wood RA, Bauza M, Krupic J, Burton S, Delekate A, Chan D, O'Keefe J
Published by:
Nature (554: 102-105) (doi: 10.1038/nature25433)
24 January 2018

Fully integrated silicon probes for high-density recording of neural activity

Jun J, Steinmetz N, Siegle J et al.
Published by:
Nature (551: 232–236) (doi: 10.1038/nature24636)
09 November 2017

Grid cell symmetry is shaped by environmental geometry

Krupic J, Bauza M, Burton S, Barry C, O’Keefe J
Published by:
Nature (518(7538): 232-5) (doi: 10.1038/nature14153)
11 February 2015

How vision and movement combine in the hippocampal place code

Chen G, King J, Burgess N, O'Keefe J
Published by:
PNAS (110: 378–383) (doi: 10.1073/pnas.1215834110)
02 January 2013

Development of the hippocampal cognitive map in preweaning rats

Wills TJ, Cacucci F, Burgess N, O’Keefe J
Published by:
Science (328: 1573-1576) (doi: 10.1126/science.1188224)
18 June 2010

Place units in the hippocampus of the freely moving rat

O'Keefe J
Published by:
Experimental Neurology (51: 78-109) (doi: 10.1016/0014-4886(76)90055-8)
01 April 1976

The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat

O'Keefe J, Dostrovsky J
Published by:
Brain Research (34: 171-175) (doi: 10.1016/0006-8993(71)90358-1)
01 November 1971