Y a-t il un pilote dans le cerveau? Données récentes Sur les bases neuronales de l orientation spatiale

Transcription

1 Laboratory of Cognitive Neuroscience, Marseille NeuroSTIC Grenoble, June 23 24, 2016 Y a-t il un pilote dans le cerveau? Données récentes Sur les bases neuronales de l orientation spatiale

2 Why is it important to have good orientation skills? LAB TRAIN STATION Canebière Vieux-Port Notre Dame de la garde

3 Why is it important to have good orientation skills? LAB TRAIN STATION Canebière Vieux-Port Notre Dame de la garde

4 Why is it important to have good orientation skills? LAB TRAIN STATION Canebière Vieux-Port Notre Dame de la garde

5 What do we need to find our path? Know current location in space Locate the goal(s) Plan the path(s) to the goal(s) These functions rely on a memory representation of space or «cognitive map». This cognitive map contains information about places in the environment and their spatial relationships. It allows the organism to generate direct paths as well as to flexibly change its path when necessary (i.e. to take shortcuts or make detours).

6 What are the neural bases of spatial representations? Some pathological brain conditions may alter spatial representations and lead to desorientation.

7 Neural bases of spatial navigation in animals Orienting in space is crucial for survival Animal behavior reveals the existence of several navigation strategies Overall organization of the mammal brain is conserved across species Multi-level approach (systems, neural populations, single neurons, synaptic and cellular levels)

8 Neural bases of spatial navigation in animals Spatial navigation is the ability to display optimal paths in space based on a representation of places and their spatial relationships.

9 Outline of talk Spatial navigation and spatial information processing Place cell firing during simple exploration Place cell firing during spatial navigation Conclusion

10 Spatial navigation and spatial information processing Behavioral strategies Allocentric strategy Egocentric strategy Self-positioning and goal localization based on external (allothetic) cues Goal localization based on self-motion (idiothetic) cues

11 Neural bases of spatial navigation Spatial navigation relies on a diversity of cognitive processes (self-localization, spatial memory, planning ) and therefore a number of brain structures. retrosplenial cortex prefrontal cortex parietal cortex visual cortex Striatum hippocampus place cells entorhinal cortex

12 Neural bases of spatial navigation Methods Looking at learning and performance of spatial tasks Looking at electrophysiological activity Interfering with normal activity of specific brain regions

13 Place cell firing during simple exploration Hippocampal place cells code rat s current location

14 Place cell firing during simple exploration Collective representation of space by place fields Different place fields Long-term stability of place fields D Day 1 Day 10 Place fields are controlled by environmental cues

15 Place cell firing during simple exploration Learning a new map Place fields are specific to each environment (orthogonal representations) D Cell 1 Cell 2 Cell 3

16 Place cell firing during simple exploration Learning a new map Zif268 is a transcription factor that plays a crucial role in late phase LTP and consolidation of spatial memories Mutant mice zif268 -/- Renaudineau et al. (2009)

17 Place cell firing during simple exploration Learning a new map Zif268 is a transcription factor that plays a crucial role in late phase LTP and consolidation of spatial memories Day 1 Day 2 Familiar Novel Familiar Experienced on Day 1 Mutant mice zif268 -/- Wild type mice Same zif268 mice Different Long-term stability of place cell representations requires transcription dependent mechanisms similar to those observed in LTP. Renaudineau et al. (2009)

18 Place cell firing during simple exploration Overdispersion obs = 37 exp = 29 obs = 5 exp = 27 Z = Z = Z = (obs-exp)/ (exp) Fenton and Muller (1998)

19 Place cells and spatial navigation After 12 training trials After 24 training trials X Control Hippocampal Hippocampal lesions block spatial learning

20 Alvernhe et al. (2008) Place cell firing during spatial navigation Effects of local changes : Shortcuts Session 1 Session 2 (shortcut) Session 3 Far field Near field

21 Navigation properties of place cells Coding of spatial sequences Place cells represent positions other than the rat s current location Replay (Wilson et al., 2001, 2002, 2006) -> sequence coding Sweep ahead (Johnson & Redish, 2007) -> decision making Preplay of future place cell sequences and planning (Pfeiffer & Foster, 2013)

22 Lenck-Santini et al. (2002); Hok et al. (2005, 2007, 2013) Place cell firing during spatial navigation A navigation task compatible with unit recordings E Duvelle On each correct response, a food pellet is delivered whose final location can be everywhere in the cylinder. Thus, it is possible to both sample unit activity everywhere in the cylinder and examine rat s performance of a place navigation task.

23 Place cell firing during spatial navigation Overdispersion c d e obs = 37 exp = 29 obs = 5 exp = 27 Z = Z = Z = (obs-exp)/ (exp) Fenton et al. (2010)

24 Place cell firing during spatial navigation Overdispersion An effect of navigation strategy? Allothetic (environmental) cues Idiothetic (self-motion) cues

25 Fenton et al. (2010) Place cell firing during spatial navigation Overdispersion Overdispersion is reduced when the rat has to pay attention to one set of cues Both allothetic and idiothetic cues are available Only allothetic cues are useful

26 Nb correct resp. Nb correct resp. Lenck-Santini et al. (2002) Place cell firing during spatial navigation Place cell information is important for place navigation but for not cue navigation Place task Cue task Correct Incorrect Correct Incorrect

27 Hok et al. (2007) Place cell firing during spatial navigation Do place cells code only space? Firing rate maps of 12 distinct place cells Rat at goal for 2s It is still unclear what goal-related firing stands for: Time? Space? Reward expectation?

28 Place cells and prefrontal cortex Place cell firing carries information useful for the rat s navigation behavior through both widely distributed place fields and focal goal-related activity. In contrast, many cells in the frontal cortex fire mostly at goal locations. In addition, their goal fields are extended, which might provide the basis for coarse coding of spatial goals. goal zone Prefrontal cortex Parietal cortex Retrosplenial cortex Visual cortex Hippocampus Entorhinal cortex Distribution of place fields in the hippocampus Distribution of goal fields in frontal cortex Hok et al. (2007) Hok et al. (2005) From Gaussier et al., 2002

29 Hok et al., J. Neurosci. (2013) Place cells and prefrontal cortex Effects of prefrontal cortex inactivation on place cell firing Behavior Unit activity and local field potentials

30 Hok et al., J. Neurosci. (2013) Place cells and prefrontal cortex Effects of prefrontal cortex inactivation on place cell firing Unit activity and overdispersion Saline s 2 = 3.62 *** Lidocaine s 2 = 2.13

31 The network of rat brain regions carrying spatial signals Visual cortex Prefrontal cortex Hippocampus Subiculum Entorhinal cortex Postsubiculum Retrosplenial cortex Anterior dorsal thalamic nuclei Dorsal striatum Parasubiculum Hippocampus Lateral dorsal thalamus Lateral mammillary nuclei Entorhinal cortex Dorsal tegmentum Medial vestibular nuclei Head directional cells Place cells Goal cells Grid cells, direction, conjoint, border cells

32 What about the human hippocampus? Memory properties Configural coding (excellent for spatial configurations ) Fast coding (one-trial learning)

33 What about the human hippocampus? Navigation properties Navigation in a virtual environment is impaired in patients with hippocampal lesions Posterior hippocampus is larger in good navigators (taxi drivers) than in control people Hippocampus is selectively activated during a mental navigation task

34 What about the human hippocampus? Navigation properties Unit activity in the hippocampus during a virtual navigation task resembles place cell firing Ekstrom et al. (2003)

35 Conclusions Hippocampal place cells provide the animal with a spatial map of the environment which is used for spatial navigation. Place cells are part of a extended neural network whose function is to provide the animal with positional and directional information. The frontal cortex may exert a possible drive on place cells by modulating attention to sensory cues.

36 Acknowledgements A. Alvernhe, Aix-Marseille Université E. Duvelle, University College London, UK A. Fenton, New York University, USA P. Gaussier, Université de Cergy-Pontoise V. Hok, Aix-Marseille Université P.P. Lenck-Santini, Aix-Marseille Université R.U. Muller, SUNY Brooklyn, USA F. Sargolini, Aix-Marseille Université E. Save, Aix-Marseille Université