Lesions of the dorsal tegmental nuclei disrupt control of navigation by distal landmarks in cued, directional, and place variants of the Morris water task.

Navigation depends on a network of neural systems that accurately monitor an animal's spatial orientation in an environment. Within this navigation system are head direction (HD) cells which discharge as a function of an animal's directional heading, providing an animal with a neural compass to guide ongoing spatial behavior. Experiments were designed to test this hypothesis by damaging the dorsal tegmental nucleus (DTN), a midbrain structure that plays a critical role in the generation of the rodent HD cell signal, and evaluating landmark based navigation using variants of the Morris water task. In Experiments 1 and 2, shams and DTN-lesioned rats were trained to navigate toward a cued platform in the presence of a constellation of distal landmarks located outside the pool. After reaching a training criteria, rats were tested in three probe trials in which (a) the cued platform was completely removed from the pool, (b) the pool was repositioned and the cued platform remained in the same absolute location with respect to distal landmarks, or (c) the pool was repositioned and the cued platform remained in the same relative location in the pool. In general, DTN-lesioned rats required more training trials to reach performance criterion, were less accurate to navigate to the platform position when it was removed, and navigated directly to the cued platform regardless of its position in the pool, indicating a general absence of control over navigation by distal landmarks. In Experiment 3, DTN and control rats were trained in directional and place navigation variants of the water task where the pool was repositioned for each training trial and a hidden platform was placed either in the same relative location (direction) in the pool or in the same absolute location (place) in the distal room reference frame. DTN-lesioned rats were initially impaired in the direction task, but ultimately performed as well as controls. In the place task, DTN-lesioned rats were severely impaired and displayed little evidence of improvement over the course of training. Together, these results support the conclusion that the DTN is required for accurate landmark navigation.

[1]  R. Sutherland,et al.  Place navigation by rats in a swimming pool. , 1984 .

[2]  J. T. Erichsen,et al.  Selective lamina dysregulation in granular retrosplenial cortex (area 29) after anterior thalamic lesions: an in situ hybridization and trans-neuronal tracing study in rats , 2010, Neuroscience.

[3]  E. Save,et al.  Evidence for entorhinal and parietal cortices involvement in path integration in the rat , 2004, Experimental Brain Research.

[4]  P. E. Sharp,et al.  Lesions of the mammillary body region severely disrupt the cortical head direction, but not place cell signal , 2008, Hippocampus.

[5]  Jeffrey S. Taube,et al.  Origins of landmark encoding in the brain , 2011, Trends in Neurosciences.

[6]  Benjamin J Clark,et al.  Deficits in landmark navigation and path integration after lesions of the interpeduncular nucleus. , 2009, Behavioral neuroscience.

[7]  Derek A. Hamilton,et al.  Control of rodent and human spatial navigation by room and apparatus cues , 2009, Behavioural Processes.

[8]  H. Blodgett,et al.  Spatial learning in the T-maze; the influence of direction, turn, and food location. , 1949, Journal of experimental psychology.

[9]  D. M. Skinner,et al.  Rats' orientation is more important than start point location for successful place learning. , 2010, Journal of experimental psychology. Animal behavior processes.

[10]  J. Taube,et al.  Lesions of the rat postsubiculum impair performance on spatial tasks. , 1992, Behavioral and neural biology.

[11]  T. Hafting,et al.  Microstructure of a spatial map in the entorhinal cortex , 2005, Nature.

[12]  Sidney B. Williams,et al.  Directional Responding of C57BL/6J Mice in the Morris Water Maze Is Influenced by Visual and Vestibular Cues and Is Dependent on the Anterior Thalamic Nuclei , 2012, The Journal of Neuroscience.

[13]  I. Whishaw,et al.  Sequential control of navigation by locale and taxon cues in the Morris water task , 2004, Behavioural Brain Research.

[14]  D. M. Skinner,et al.  Where am I? Distal cues use requires sensitivity to start location change in the rat. , 2007, Journal of experimental psychology. Animal behavior processes.

[15]  K. Zyo,et al.  Comparative anatomical study of the tegmentomammillary projections in some mammals: A horseradish peroxidase study , 1984, Brain Research.

[16]  R. Morris,et al.  Dissociation between components of spatial memory in rats after recovery from the effects of retrohippocampal lesions , 2004, Experimental Brain Research.

[17]  J. Taube,et al.  Behavioral/systems/cognitive Hippocampal Place Cell Instability after Lesions of the Head Direction Cell Network , 2022 .

[18]  David Wirtshafter,et al.  Evidence for GABAergic projections from the tegmental nuclei of Gudden to the mammillary body in the rat , 1993, Brain Research.

[19]  P E Sharp,et al.  The Anterior Thalamic Head-Direction Signal Is Abolished by Bilateral But Not Unilateral Lesions of the Lateral Mammillary Nucleus , 1999, The Journal of Neuroscience.

[20]  M. Moser,et al.  Spatial Memory in the Rat Requires the Dorsolateral Band of the Entorhinal Cortex , 2005, Neuron.

[21]  Emilio Kropff,et al.  Place cells, grid cells, and the brain's spatial representation system. , 2008, Annual review of neuroscience.

[22]  J. Pearce,et al.  Interaction between piloting and beacon homing by rats in a swimming pool. , 1997, Journal of experimental psychology. Animal behavior processes.

[23]  I. Whishaw,et al.  Homing with locale, taxon, and dead reckoning strategies by foraging rats: sensory hierarchy in spatial navigation , 1999, Behavioural Brain Research.

[24]  Travis E. Johnson,et al.  Delayed development of place navigation compared to directional responding in young rats. , 2009, Behavioral neuroscience.

[25]  Seralynne D Vann,et al.  Transient spatial deficit associated with bilateral lesions of the lateral mammillary nuclei , 2005, The European journal of neuroscience.

[26]  Douglas G Wallace,et al.  Quantification of a single exploratory trip reveals hippocampal formation mediated dead reckoning , 2002, Journal of Neuroscience Methods.

[27]  Bruce L. McNaughton,et al.  Path integration and the neural basis of the 'cognitive map' , 2006, Nature Reviews Neuroscience.

[28]  J. Knierim,et al.  Framing spatial cognition: neural representations of proximal and distal frames of reference and their roles in navigation. , 2011, Physiological reviews.

[29]  J. O'Keefe,et al.  The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. , 1971, Brain research.

[30]  J. Prados,et al.  Locating an invisible goal in a water maze requires at least two landmarks , 1998, Psychobiology.

[31]  J. Taube,et al.  Effects of repeated disorientation on the acquisition of spatial tasks in rats: dissociation between the appetitive radial arm maze and aversive water maze. , 1997, Journal of experimental psychology. Animal behavior processes.

[32]  Rebecca Burwell,et al.  Severity of spatial learning impairment in aging: Development of a learning index for performance in the Morris water maze. , 1993, Behavioral neuroscience.

[33]  D. M. Skinner,et al.  An analysis of response, direction, and place learning in an open field and T maze. , 2003, Journal of experimental psychology. Animal behavior processes.

[34]  W E Skaggs,et al.  Deciphering the hippocampal polyglot: the hippocampus as a path integration system. , 1996, The Journal of experimental biology.

[35]  Travis E. Johnson,et al.  Evidence for a shift from place navigation to directional responding in one variant of the Morris water task. , 2009, Journal of experimental psychology. Animal behavior processes.

[36]  J. Pearce,et al.  CONTROL OF SPATIAL BEHAVIOR BY AN UNSTABLE LANDMARK , 1998 .

[37]  Seralynne D. Vann,et al.  A role for the head-direction system in geometric learning , 2011, Behavioural Brain Research.

[38]  Ariane S Etienne,et al.  Path integration in mammals , 2004, Hippocampus.

[39]  William N Butler,et al.  The Head-Direction Signal Is Critical for Navigation Requiring a Cognitive Map but Not for Learning a Spatial Habit , 2013, Current Biology.

[40]  Katherine G Akers,et al.  How do room and apparatus cues control navigation in the Morris water task? Evidence for distinct contributions to a movement vector. , 2007, Journal of experimental psychology. Animal behavior processes.

[41]  Andrew Baumann.  THE RELATIVE INFLUENCE OF , 2015 .

[42]  E. Maguire,et al.  What does the retrosplenial cortex do? , 2009, Nature Reviews Neuroscience.

[43]  Travis E. Johnson,et al.  The relative influence of place and direction in the Morris water task. , 2008, Journal of experimental psychology. Animal behavior processes.

[44]  I. Whishaw,et al.  Perseveration on place reversals in spatial swimming pool tasks: Further evidence for place learning in hippocampal rats , 1997, Hippocampus.

[45]  D. M. Skinner,et al.  The effects of hippocampal lesions on response, direction, and place learning in rats. , 2005, Behavioral neuroscience.

[46]  I. Whishaw,et al.  Hippocampectomized rats are impaired in homing by path integration , 1999, Hippocampus.

[47]  M. Gallagher,et al.  Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze. , 1993, Behavioral neuroscience.

[48]  P. Kelly,et al.  Habenula lesions cause impaired cognitive performance in rats: implications for schizophrenia , 2004, The European journal of neuroscience.

[49]  B. A. Conway,et al.  The effects of laforin, malin, Stbd1, and Ptg deficiencies on heart glycogen levels in Pompe disease mouse models , 2015 .

[50]  B. McNaughton,et al.  Dead Reckoning, Landmark Learning, and the Sense of Direction: A Neurophysiological and Computational Hypothesis , 1991, Journal of Cognitive Neuroscience.

[51]  J. Taube,et al.  Degradation of Head Direction Cell Activity during Inverted Locomotion , 2005, The Journal of Neuroscience.

[52]  H. T. Blair,et al.  The anatomical and computational basis of the rat head-direction cell signal , 2001, Trends in Neurosciences.

[53]  Derek A. Hamilton,et al.  Rodent spatial navigation: at the crossroads of cognition and movement , 2004, Neuroscience & Biobehavioral Reviews.

[54]  R. Morris.  Spatial Localization Does Not Require the Presence of Local Cues , 1981 .

[55]  P. E. Sharp,et al.  Angular velocity and head direction signals recorded from the dorsal tegmental nucleus of gudden in the rat: implications for path integration in the head direction cell circuit. , 2001, Behavioral neuroscience.

[56]  R. J. McDonald,et al.  Finding a goal on dry land and in the water: differential effects of disorientation on spatial learning , 2001, Behavioural Brain Research.

[57]  Ian Q. Whishaw,et al.  Impairments in the acquisition, retention and selection of spatial navigation strategies after medial caudate-putamen lesions in rats , 1987, Behavioural Brain Research.

[58]  Jeffrey S. Taube,et al.  Directional learning, but no spatial mapping by rats performing a navigational task in an inverted orientation , 2010, Neurobiology of Learning and Memory.

[59]  J. Aggleton,et al.  A comparison of the effects of anterior thalamic, mamillary body and fornix lesions on reinforced spatial alternation , 1995, Behavioural Brain Research.

[60]  J. Taube.  The head direction signal: origins and sensory-motor integration. , 2007, Annual review of neuroscience.

[61]  J. Aggleton,et al.  Anterior thalamic lesions stop immediate early gene activation in selective laminae of the retrosplenial cortex: evidence of covert pathology in rats? , 2004, The European journal of neuroscience.

[62]  Jeffrey S Taube,et al.  Path integration and lesions within the head direction cell circuit: comparison between the roles of the anterodorsal thalamus and dorsal tegmental nucleus. , 2006, Behavioral neuroscience.

[63]  J. D. McGaugh,et al.  Inactivation of Hippocampus or Caudate Nucleus with Lidocaine Differentially Affects Expression of Place and Response Learning , 1996, Neurobiology of Learning and Memory.

[64]  Travis E. Johnson,et al.  Cued platform training reveals early development of directional responding among preweanling rats in the Morris water task. , 2011, Developmental psychobiology.

[65]  C. Barnes.  Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. , 1979, Journal of comparative and physiological psychology.

[66]  Bryan Kolb,et al.  Spatial mapping: definitive disruption by hippocampal or medial frontal cortical damage in the rat , 1982, Neuroscience Letters.

[67]  Jeffrey S. Taube,et al.  Vestibular and attractor network basis of the head direction cell signal in subcortical circuits , 2012, Front. Neural Circuits.

[68]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[69]  G. M. Martin,et al.  Spatial disorientation blocks reliable goal location on a plus maze but does not prevent goal location in the Morris maze. , 1997, Journal of experimental psychology. Animal behavior processes.

[70]  Jonathan D. Cohen,et al.  Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex , 2006 .

[71]  Matthew L. Tullman,et al.  Lesions of the Tegmentomammillary Circuit in the Head Direction System Disrupt the Head Direction Signal in the Anterior Thalamus , 2007, The Journal of Neuroscience.

[72]  C. Gallistel.  The organization of learning , 1990 .

[73]  J. Bassett,et al.  Neural Correlates for Angular Head Velocity in the Rat Dorsal Tegmental Nucleus , 2001, The Journal of Neuroscience.

[74]  J. O’Keefe,et al.  An oscillatory interference model of grid cell firing , 2007, Hippocampus.

[75]  D. M. Skinner,et al.  An assessment of response, direction and place learning by rats in a water T-maze , 2009 .

[76]  R. Morris.  Developments of a water-maze procedure for studying spatial learning in the rat , 1984, Journal of Neuroscience Methods.

[77]  P. E. Sharp,et al.  Lesions of the mammillary body region alter hippocampal movement signals and theta frequency: Implications for path integration models , 2008, Hippocampus.

[78]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[79]  B. McNaughton,et al.  Place cells, head direction cells, and the learning of landmark stability , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[80]  H. T. Blair,et al.  Role of the Lateral Mammillary Nucleus in the Rat Head Direction Circuit A Combined Single Unit Recording and Lesion Study , 1998, Neuron.

[81]  Rudolf Jander,et al.  Short-range homing in the house mouse, Mus musculus: stages in the learning of directions , 1994, Animal Behaviour.

[82]  A. Gonzalo-Ruiz,et al.  Immunohistochemical localization of gaba in the mammillary complex of the rat , 1993, Neuroscience.

[83]  K. Zyo,et al.  Fine structure of the lateral mammillary projection to the dorsal tegmental nucleus of gudden in the rat , 1990, The Journal of comparative neurology.