Anatomical and physiological foundations of cerebello-hippocampal interaction

Multiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such communication remains unknown. Using rabies virus as a retrograde transneuronal tracer in mice, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally suggest that the two structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6–12 Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.

[1]  Laure Rondi-Reig,et al.  Is the cerebellum ready for navigation? , 2005, Progress in brain research.

[2]  L. Vinay,et al.  Characterization of last‐order premotor interneurons by transneuronal tracing with rabies virus in the neonatal mouse spinal cord , 2011, The Journal of comparative neurology.

[3]  R. Buckner The Cerebellum and Cognitive Function: 25 Years of Insight from Anatomy and Neuroimaging , 2013, Neuron.

[4]  Daniela Popa,et al.  Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements , 2014, Nature Neuroscience.

[5]  Freek E. Hoebeek,et al.  Causes and Consequences of Oscillations in the Cerebellar Cortex , 2008, Neuron.

[6]  P. P. Newman,et al.  Functional relationships between the hippocampus and the cerebellum: an electrophysiological study of the cat. , 1979, The Journal of physiology.

[7]  D. Armstrong,et al.  Olivo‐cortico‐nuclear localizations within crus I of the cerebellum , 2006, The Journal of comparative neurology.

[8]  D. Woodward,et al.  The pontocerebellar system in the rat: An HRP study. I. Posterior vermis , 1981, The Journal of comparative neurology.

[9]  M. Molinari,et al.  The cerebellum in the spatial problem solving: a co-star or a guest star? , 1998, Progress in Neurobiology.

[10]  M. Barrot,et al.  Clusters of cerebellar Purkinje cells control their afferent climbing fiber discharge , 2013, Proceedings of the National Academy of Sciences.

[11]  C. Stam,et al.  Phase lag index: Assessment of functional connectivity from multi channel EEG and MEG with diminished bias from common sources , 2007, Human brain mapping.

[12]  Karim Benchenane,et al.  Explicit memory creation during sleep demonstrates a causal role of place cells in navigation , 2015, Nature Neuroscience.

[13]  Li Yang,et al.  Theta synchronization between medial prefrontal cortex and cerebellum is associated with adaptive performance of associative learning behavior , 2016, Scientific Reports.

[14]  Guy Mittleman,et al.  Connecting the dots of the cerebro‐cerebellar role in cognitive function: Neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex , 2011, Synapse.

[15]  Richard Apps,et al.  Back to front: cerebellar connections and interactions with the prefrontal cortex , 2014, Front. Syst. Neurosci..

[16]  N. Ramnani The primate cortico-cerebellar system: anatomy and function , 2006, Nature Reviews Neuroscience.

[17]  Nicolas Brunel,et al.  Electrical Coupling Mediates Tunable Low-Frequency Oscillations and Resonance in the Cerebellar Golgi Cell Network , 2009, Neuron.

[18]  J M Bower,et al.  Oscillatory activity in the cerebellar hemispheres of unrestrained rats. , 1998, Journal of neurophysiology.

[19]  I. Sugihara Compartmentalization of the Deep Cerebellar Nuclei Based on Afferent Projections and Aldolase C Expression , 2011, The Cerebellum.

[20]  Laure Rondi-Reig,et al.  A hippocampo-cerebellar centred network for the learning and execution of sequence-based navigation , 2017, Scientific Reports.

[21]  E. Save,et al.  Cerebellum Shapes Hippocampal Spatial Code , 2011, Science.

[22]  P. Strick,et al.  Activation of a cerebellar output nucleus during cognitive processing. , 1994, Science.

[23]  P. Strick,et al.  Rabies as a transneuronal tracer of circuits in the central nervous system , 2000, Journal of Neuroscience Methods.

[24]  Masao Ito,et al.  Consensus Paper: The Cerebellum's Role in Movement and Cognition , 2013, The Cerebellum.

[25]  R. Snider,et al.  Some Cerebellar Influences on Electrically‐Induced Cerebral Seizures * , 1955, Epilepsia.

[26]  R. Snider,et al.  Cerebello-hippocampal influences on the electroencephalogram. , 1959, Electroencephalography and clinical neurophysiology.

[27]  P. Strick,et al.  The cerebellum communicates with the basal ganglia , 2005, Nature Neuroscience.

[28]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[29]  R. Hawkes,et al.  Zebrin II: A polypeptide antigen expressed selectively by purkinje cells reveals compartments in rat and fish cerebellum , 1990, The Journal of comparative neurology.

[30]  P. Strick,et al.  Macro-architecture of basal ganglia loops with the cerebral cortex: use of rabies virus to reveal multisynaptic circuits. , 2004, Progress in brain research.

[31]  Richard Hawkes,et al.  Conservation of the architecture of the anterior lobe vermis of the cerebellum across mammalian species. , 2005, Progress in brain research.

[32]  Thomas Klausberger,et al.  Hippocampal Place Cells Couple to Three Different Gamma Oscillations during Place Field Traversal , 2016, Neuron.

[33]  Hao Chen,et al.  Baseline theta activities in medial prefrontal cortex and deep cerebellar nuclei are associated with the extinction of trace conditioned eyeblink responses in guinea pigs , 2014, Behavioural Brain Research.

[34]  W. Skaggs,et al.  The Cerebellum , 2016 .

[35]  Richard Apps,et al.  Lateral cerebellum: functional localization within crus I and correspondence to cortical zones , 2003, The European journal of neuroscience.

[36]  Wolf Singer,et al.  Neuronal Synchrony: A Versatile Code for the Definition of Relations? , 1999, Neuron.

[37]  T. Babb,et al.  Fastigiobulbar and dentatothalamic influences on hippocampal cobalt epilepsy in the cat. , 1974, Electroencephalography and clinical neurophysiology.

[38]  Mary Beth Nebel,et al.  Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice , 2017, Nature Neuroscience.

[39]  G. Cheron,et al.  Oscillations, Timing, Plasticity, and Learning in the Cerebellum , 2015, The Cerebellum.

[40]  F. Sultan,et al.  Functional localization in the cerebellum , 2011, Cortex.

[41]  Tomaso Muzzu,et al.  Encoding of locomotion kinematics in the mouse cerebellum , 2016, bioRxiv.

[42]  J. Voogd,et al.  Topography of cerebellar nuclear projections to the brain stem in the rat. , 2000, Progress in brain research.

[43]  W. Carlezon,et al.  Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation , 2007, Nature Protocols.

[44]  P. May,et al.  Neuronal connections between the cerebellar nuclei and hypothalamus in Macaca fascicularis: Cerebello‐visceral circuits , 1990, The Journal of comparative neurology.

[45]  Robert Oostenveld,et al.  An improved index of phase-synchronization for electrophysiological data in the presence of volume-conduction, noise and sample-size bias , 2011, NeuroImage.

[46]  C. Schroeder,et al.  How Local Is the Local Field Potential? , 2011, Neuron.

[47]  Laure Rondi-Reig,et al.  Impaired cerebellar Purkinje cell potentiation generates unstable spatial map orientation and inaccurate navigation , 2019, Nature Communications.

[48]  G. Ugolini,et al.  Advances in viral transneuronal tracing , 2010, Journal of Neuroscience Methods.

[49]  Catherine J. Stoodley,et al.  Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing , 2010, Cortex.

[50]  Andreea C. Bostan,et al.  The basal ganglia communicate with the cerebellum , 2010, Proceedings of the National Academy of Sciences.

[51]  Richard Apps,et al.  An internal model of a moving visual target in the lateral cerebellum , 2009, The Journal of physiology.

[52]  T. Ruigrok,et al.  Disynaptic Subthalamic Input to the Posterior Cerebellum in Rat , 2017, Front. Neuroanat..

[53]  Laure Rondi-Reig,et al.  How the cerebellum may monitor sensory information for spatial representation , 2014, Front. Syst. Neurosci..

[54]  Partha P. Mitra,et al.  Chronux: A platform for analyzing neural signals , 2010, Journal of Neuroscience Methods.

[55]  Rune W. Berg,et al.  Coherent electrical activity between vibrissa sensory areas of cerebellum and neocortex is enhanced during free whisking. , 2002, Journal of neurophysiology.

[56]  E. Moser,et al.  Faculty Opinions recommendation of Entrainment of neocortical neurons and gamma oscillations by the hippocampal theta rhythm. , 2009 .

[57]  Athanassios G. Siapas,et al.  Structured Variability in Purkinje Cell Activity during Locomotion , 2015, Neuron.

[58]  P. Strick,et al.  Cerebellar Loops with Motor Cortex and Prefrontal Cortex of a Nonhuman Primate , 2003, The Journal of Neuroscience.

[59]  Jan Voogd,et al.  Oculomotor cerebellum. , 2006, Progress in brain research.

[60]  M. Penttonen,et al.  Hippocampo–cerebellar theta band phase synchrony in rabbits , 2010, Neuroscience.

[61]  P. Fries A mechanism for cognitive dynamics: neuronal communication through neuronal coherence , 2005, Trends in Cognitive Sciences.

[62]  A. Berthoz,et al.  Spatial navigation impairment in mice lacking cerebellar LTD: a motor adaptation deficit? , 2005, Nature Neuroscience.

[63]  G. Buzsáki,et al.  Memory, navigation and theta rhythm in the hippocampal-entorhinal system , 2013, Nature Neuroscience.

[64]  K. Khodakhah,et al.  Short latency cerebellar modulation of the basal ganglia , 2014, Nature Neuroscience.

[65]  R. Heath,et al.  Cerebellar stimulation: effects on septal region, hippocampus, and amygdala of cats and rats. , 1978, Biological psychiatry.

[66]  Kamran Khodakhah,et al.  Cerebellar modulation of the reward circuitry and social behavior , 2019, Science.

[67]  Izumi Sugihara,et al.  Identification of aldolase C compartments in the mouse cerebellar cortex by olivocerebellar labeling , 2007, The Journal of comparative neurology.

[68]  Sean M Montgomery,et al.  Entrainment of Neocortical Neurons and Gamma Oscillations by the Hippocampal Theta Rhythm , 2008, Neuron.

[69]  M. Wilson,et al.  Theta Rhythms Coordinate Hippocampal–Prefrontal Interactions in a Spatial Memory Task , 2005, PLoS biology.

[70]  R. Snider,et al.  Septal afterdischarges and their modification by the cerebellum , 1975, Experimental Neurology.

[71]  Sho Aoki,et al.  Multizonal Cerebellar Influence Over Sensorimotor Areas of the Rat Cerebral Cortex , 2019, Cerebral cortex.

[72]  R. Snider,et al.  Relation of cerebellum to upper brain stem. , 1953, Journal of neurophysiology.

[73]  S. Baker,et al.  Cortico-cerebellar coherence during a precision grip task in the monkey. , 2006, Journal of neurophysiology.

[74]  I. Soltesz,et al.  Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy , 2014, eNeuro.

[75]  J. Taube,et al.  Hippocampal spatial representations require vestibular input , 2002, Hippocampus.

[76]  D. Jaeger,et al.  Cortico-cerebellar coherence and causal connectivity during slow-wave activity , 2010, Neuroscience.

[77]  G. Anastasi,et al.  Constrained spherical deconvolution analysis of the limbic network in human, with emphasis on a direct cerebello-limbic pathway , 2014, Front. Hum. Neurosci..

[78]  T. Ruigrok Ins and Outs of Cerebellar Modules , 2010, The Cerebellum.

[79]  Richard Apps,et al.  Cerebellar cortical organization: a one-map hypothesis , 2009, Nature Reviews Neuroscience.

[80]  C. Chapman,et al.  Diurnal influences on electrophysiological oscillations and coupling in the dorsal striatum and cerebellar cortex of the anesthetized rat , 2014, Front. Syst. Neurosci..

[81]  M. A. Basso,et al.  Circuits for Action and Cognition: A View from the Superior Colliculus. , 2017, Annual review of vision science.

[82]  Yiwen Zheng,et al.  Long‐term deficits on a foraging task after bilateral vestibular deafferentation in rats , 2009, Hippocampus.

[83]  M. Hallett,et al.  Identifying true brain interaction from EEG data using the imaginary part of coherency , 2004, Clinical Neurophysiology.

[84]  Neil G. Harris,et al.  Optogenetic fMRI and electrophysiological identification of region-specific connectivity between the cerebellar cortex and forebrain , 2018, NeuroImage.

[85]  R. Heath,et al.  Histochemical demonstration of a direct pathway from the fastigial nucleus to the septal region. , 1973, Experimental neurology.

[86]  R. Snider,et al.  Cerebellar contributions to the papez circuit , 1976, Journal of neuroscience research.

[87]  Esther Krook-Magnuson,et al.  Cognitive Collaborations: Bidirectional Functional Connectivity Between the Cerebellum and the Hippocampus , 2015, Front. Syst. Neurosci..

[88]  Matthew W. Jones,et al.  Electrophysiological Mapping of Novel Prefrontal – Cerebellar Pathways , 2009, Front. Integr. Neurosci..

[89]  Paul F. Smith,et al.  Locomotor and exploratory behavior in the rat following bilateral vestibular deafferentation. , 2008, Behavioral neuroscience.

[90]  Y. D. van der Werf,et al.  Hippocampal-cerebellar interaction during spatio-temporal prediction. , 2015, Cerebral cortex.

[91]  Yves Lamarre,et al.  Local field potential oscillations in primate cerebellar cortex: synchronization with cerebral cortex during active and passive expectancy. , 2005, Journal of neurophysiology.

[92]  D. Woodward,et al.  The pontocerebellar system in the rat: An HRP study. II. Hemispheral components , 1981, The Journal of comparative neurology.

[93]  H. Raux,et al.  Mapping of monoclonal antibody epitopes of the rabies virus P protein. , 1997, The Journal of general virology.

[94]  L. Colgin Mechanisms and functions of theta rhythms. , 2013, Annual review of neuroscience.

[95]  Y. Shinoda,et al.  Molecular, Topographic, and Functional Organization of the Cerebellar Cortex: A Study with Combined Aldolase C and Olivocerebellar Labeling , 2004, The Journal of Neuroscience.

[96]  T. Ruigrok,et al.  Organization of Cerebral Projections to Identified Cerebellar Zones in the Posterior Cerebellum of the Rat , 2012, The Journal of Neuroscience.

[97]  Christian F. Doeller,et al.  Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not Place-Based Navigation. , 2015, Cerebral cortex.

[98]  Richard Apps,et al.  Behavioural Significance of Cerebellar Modules , 2010, The Cerebellum.

[99]  Thomas D. Mrsic-Flogel,et al.  Cerebellar contribution to preparatory activity in motor neocortex , 2018 .

[100]  Richard Apps,et al.  Columnar organisation of the inferior olive projection to the posterior lobe of the rat cerebellum , 1990, The Journal of comparative neurology.

[101]  Andreea C. Bostan,et al.  The basal ganglia and the cerebellum: nodes in an integrated network , 2018, Nature Reviews Neuroscience.

[102]  R G Heath,et al.  Anatomic connections of the fastigial nucleus to the rostral forebrain in the cat. , 1973, Experimental neurology.

[103]  V Taglietti,et al.  Theta-Frequency Bursting and Resonance in Cerebellar Granule Cells: Experimental Evidence and Modeling of a Slow K+-Dependent Mechanism , 2001, The Journal of Neuroscience.

[104]  L. C. Hoffmann,et al.  Cerebellar theta oscillations are synchronized during hippocampal theta-contingent trace conditioning , 2009, Proceedings of the National Academy of Sciences.