High frequency stimulation of the posterior hypothalamic nucleus restores movement and reinstates hippocampal–striatal theta coherence following haloperidol-induced catalepsy

Deep brain stimulation (DBS) of the subthalamic nucleus has been used extensively in the treatment of Parkinson's disease. However, the efficacy of such treatments on bradykinesia/akinesia remains low. DBS of the posterior hypothalamic nucleus (PH) elicits spontaneous, non-stereotypical motor behaviours. We tested the hypothesis that PH stimulation could restore movement in animals made cataleptic by the D(2) receptor antagonist haloperidol. We further hypothesized that hippocampal-striatal neural synchrony may be important in the organization of motor behaviours. Animals chronically implanted with hippocampal and striatal recording electrodes and PH stimulating electrode were tested in open field, catalepsy and active avoidance paradigms. The degree of hippocampal-striatal theta (5-10 Hz) field coherence was assessed during baseline avoidance testing and following the administration of haloperidol. Haloperidol abolished movement in open field and active avoidance tasks and increased the latency to respond in the catalepsy test. Stimulation of the PH under haloperidol reversed catalepsy. Hippocampal-striatal theta coherence was high throughout the active avoidance task in control experiments but was greatly reduced under haloperidol. PH stimulation was able to reinstate the hippocampal-striatal theta coherence while restoring task-related behaviours. These results support the hypothesis that DBS of the PH could restore motor behaviours in rats made cataleptic with haloperidol, thus providing strong support for the PH as a promising candidate for DBS in the treatment of Parkinson's disease. Furthermore, the results support the view that hippocampal-striatal theta coherence may be important for the planning and execution of goal-oriented behaviors.

[1]  A. Michael,et al.  Voltammetry of extracellular dopamine in rat striatum during ICSS-like electrical stimulation of the medial forebrain bundle , 1993, Brain Research.

[2]  R. Vertes,et al.  Descending projections of the posterior nucleus of the hypothalamus: Phaseolus vulgaris leucoagglutinin analysis in the rat , 1996, The Journal of comparative neurology.

[3]  M. Amalric,et al.  High frequency stimulation of the subthalamic nucleus has beneficial antiparkinsonian effects on motor functions in rats, but less efficiency in a choice reaction time task , 2003, The European journal of neuroscience.

[4]  P. Mitra,et al.  Learning-related coordination of striatal and hippocampal theta rhythms during acquisition of a procedural maze task , 2007, Proceedings of the National Academy of Sciences.

[5]  H. M. Sinnamon,et al.  Locomotor stepping initiated by glutamate injections into the hypothalamus of the anesthetized rat. , 1990, Behavioral neuroscience.

[6]  Ying Liu,et al.  High frequency deep brain stimulation: What are the therapeutic mechanisms? , 2008, Neuroscience & Biobehavioral Reviews.

[7]  B. H. Bland,et al.  To move or not: Previous experience in a runway avoidance task determines the appearance of hippocampal Type 2 sensory processing theta , 2007, Behavioural Brain Research.

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

[9]  Y. Goshima,et al.  An l-DOPAergic relay from the posterior hypothalamic nucleus to the rostral ventrolateral medulla and its cardiovascular function in anesthetized rats , 1999, Neuroscience.

[10]  S. Barman.  Descending projections of hypothalamic neurons with sympathetic nerve-related activity. , 1990, Journal of neurophysiology.

[11]  B. H. Bland,et al.  Theta band oscillation and synchrony in the hippocampal formation and associated structures: the case for its role in sensorimotor integration , 2001, Behavioural Brain Research.

[12]  J. Gray.  The neuropsychology of anxiety. , 1985, Issues in mental health nursing.

[13]  A. Loewy,et al.  L-Glutamate mapping of cardioreactive areas in the rat posterior hypothalamus , 1990, Brain Research.

[14]  C. H. Vanderwolf,et al.  Hippocampal electrical activity and voluntary movement in the rat. , 1969, Electroencephalography and clinical neurophysiology.

[15]  M. J. Christie,et al.  Excitatory amino acid projections to the periaqueductal gray in the rat: A retrograde transport study utilizing d[3H]aspartate and [3H]GABA , 1990, Neuroscience.

[16]  Jian Li,et al.  Identification of pressor regions activated by central cholinergic stimulation in rat brain. , 1997, European journal of pharmacology.

[17]  Brian H. Bland,et al.  Basal ganglia–hippocampal interactions support the role of the hippocampal formation in sensorimotor integration , 2004, Experimental Neurology.

[18]  Stefan Kasicki,et al.  Theta-like rhythm in depth EEG activity of hypothalamic areas during spontaneous or electrically induced locomotion in the rat , 1995, Brain Research.

[19]  R. Moore,et al.  Putative excitatory amino acid projections to the suprachiasmatic nucleus in the rat , 1996, Brain Research.

[20]  J. Buccafusco,et al.  Autoradiographic comparison of muscarinic M1 and M2 binding sites in the CNS of spontaneously hypertensive and normotensive rats , 1997, Brain Research.

[21]  B. Bland,et al.  Intraseptal procaine abolishes hypothalamic stimulation-induced wheel- running and hippocampal theta field activity in rats , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  E. J. Green,et al.  Hypothalamic, midbrain and bulbar areas involved in the defense reaction in rabbits , 1991, Physiology & Behavior.

[23]  L. Hersh,et al.  Patterns of direct projections from the hippocampus to the medial septum-diagonal band complex: Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with immunohistochemistry of choline acetyltransferase , 1991, Neuroscience.

[24]  Ann M Graybiel,et al.  Oscillations of local field potentials in the rat dorsal striatum during spontaneous and instructed behaviors. , 2007, Journal of neurophysiology.

[25]  H. M. Sinnamon,et al.  Locomotor sites mapped with low current stimulation in intact and kainic acid damaged hypothalamus of anesthetized rats , 1991, Behavioural Brain Research.

[26]  W. Cowan,et al.  The connections of the septal region in the rat , 1979, The Journal of comparative neurology.

[27]  F. Luft,et al.  Hypothalamic GABA and Sympathetic Regulation in Spontaneously Hypertensive Rats , 1989, Hypertension.

[28]  N. Schneiderman,et al.  Cardiovascular responses elicited by hypothalamic stimulation in rabbits reveal a mediolateral organization. , 1981, Journal of the autonomic nervous system.

[29]  B. Balleine,et al.  Differential effects of escapable and inescapable footshock on hippocampal theta activity. , 1991, Behavioral neuroscience.

[30]  V. Sturm,et al.  Deep brain stimulation for Parkinson's disease. , 2007, Acta neurochirurgica. Supplement.

[31]  Jesse Jackson,et al.  Amplitude, frequency, and phase analysis of hippocampal theta during sensorimotor processing in a jump avoidance task , 2006, Hippocampus.

[32]  C. H. Vanderwolf,et al.  Electrical stimulation of the brain stem in freely moving rats: II. Effects on hippocampal and neocortical electrical activity, and relations to behavior , 1978, Experimental Neurology.

[33]  C. H. Vanderwolf,et al.  Two types of hippocampal rhythmical slow activity in both the rabbit and the rat: Relations to behavior and effects of atropine, diethyl ether, urethane, and pentobarbital , 1975, Experimental Neurology.

[34]  James McNames,et al.  A Biomedical Signal Processing Toolbox , 2002 .

[35]  Christos Constantinidis,et al.  Synchronous oscillations and phase reorganization in the basal ganglia during akinesia induced by high‐dose haloperidol , 2007, The European journal of neuroscience.

[36]  Liliana Garcia,et al.  High-frequency Stimulation in Parkinson's Disease: More or Less? , 2022 .

[37]  A. Siegel,et al.  The organization of the hypothalamic pathways mediating affective defense behavior in the cat , 1985, Brain Research.

[38]  Eric E. Abrahamson,et al.  The posterior hypothalamic area: chemoarchitecture and afferent connections , 2001, Brain Research.

[39]  J. B. Justice,et al.  Dynamics of the recovery of releasable dopamine following electrical stimulation of the medial forebrain bundle , 1987, Neuroscience Letters.

[40]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[41]  A. Heynen,et al.  Behavioral correlates of hippocampal type 2 theta in the rat , 1987, Physiology & Behavior.

[42]  Jozsef Csicsvari,et al.  Polytrodes: high-density silicon electrode arrays for large-scale multiunit recording. , 2005, Journal of neurophysiology.

[43]  S. Nakamura,et al.  Effect of l-glutamate, injected into the posterior hypothalamus, on blood pressure and heart rate in unanesthetized and unrestrained rats , 1985, Neuropharmacology.

[44]  R. Vertes,et al.  Ascending projections of the posterior nucleus of the hypothalamus: PHA‐L analysis in the rat , 1995, The Journal of comparative neurology.

[45]  H. Mallot,et al.  Inactivation of the rat dorsal striatum impairs performance in spatial tasks and alters hippocampal theta in the freely moving rat , 2005, Behavioural Brain Research.

[46]  H. Eichenbaum,et al.  Oscillatory Entrainment of Striatal Neurons in Freely Moving Rats , 2004, Neuron.

[47]  J. Dimicco,et al.  Defense reaction elicited by injection of GABA antagonists and synthesis inhibitors into the posterior hypothalamus in rats , 1987, Neuropharmacology.

[48]  B H Bland,et al.  Diencephalic and hippocampal mechanisms of motor activity in the rat: effects of posterior hypothalamic stimulation on behavior and hippocampal slow wave activity. , 1972, Brain research.

[49]  S. Kasicki,et al.  The frequency of rat's hippocampal theta rhythm is related to the speed of locomotion , 1998, Brain Research.

[50]  J. B. Justice,et al.  Mechanisms contributing to the recovery of striatal releasable dopamine following MFB stimulation , 1987, Brain Research.

[51]  T. Robinson,et al.  Effects of posterior hypothalamic lesions on voluntary behavior and hippocampal electroencephalograms in the rat. , 1974, Journal of comparative and physiological psychology.

[52]  John R Martin.  Neuropeptide Y potentiates the pressor response evoked by carbachol administration into the posterior hypothalamic nucleus of conscious rat , 2002, Brain Research.

[53]  M. Hasselmo.  What is the function of hippocampal theta rhythm?—Linking behavioral data to phasic properties of field potential and unit recording data , 2005, Hippocampus.

[54]  B. H. Bland,et al.  The Role of the Septohippocampal Pathway in the Regulation of Hippocampal Field Activity and Behavior: Analysis by the Intraseptal Microinfusion of Carbachol, Atropine, and Procaine , 1993, Experimental Neurology.

[55]  H. M. Sinnamon,et al.  Preoptic and hypothalamic neurons and the initiation of locomotion in the anesthetized rat , 1993, Progress in Neurobiology.

[56]  G. Iwamoto,et al.  Microinjection of GABA antagonists into the posterior hypothalamus elicits locomotor activity and a cardiorespiratory activation , 1988, Brain Research.

[57]  K. Barron,et al.  Posterior hypothalamic influences on cardiovascular effects of aortic nerve stimulation. , 1989, American Journal of Physiology.

[58]  R. Gaykema,et al.  Cortical projection patterns of the medial septum‐diagonal band complex , 1990, The Journal of comparative neurology.

[59]  B. Waterhouse,et al.  Retrograde study of hypocretin-1 (orexin-A) projections to subdivisions of the dorsal raphe nucleus in the rat , 2005, Brain Research.

[60]  B. McNaughton,et al.  Reversible inactivation of the medial septum: selective effects on the spontaneous unit activity of different hippocampal cell types , 1989, Brain Research.

[61]  L. Swanson,et al.  Anatomy of the soul as reflected in the cerebral hemispheres: Neural circuits underlying voluntary control of basic motivated behaviors , 2005, The Journal of comparative neurology.

[62]  J. Buccafusco,et al.  Pharmacological study of a cholinergic mechanism within the rat posterior hypothalamic nucleus which mediates a hypertensive response , 1979, Brain Research.

[63]  A. Shekhar,et al.  Selective enhancement of shock avoidance responding elicited by GABA blockade in the posterior hypothalamus of rats , 1987, Brain Research.

[64]  J. Wible,et al.  Microinjection of GABA antagonists into posterior hypothalamus elevates heart rate in anesthetizes rats , 1986, Neuropharmacology.