Involvement of the mammillary bodies in spatial working memory revealed by cytochrome oxidase activity

In view of the inconclusive findings relating the nuclei of the mammillary bodies (MB) with spatial memory, we evaluated the oxidative metabolic activity of the medial and lateral nuclei of the mammillary bodies (MB) after training young rats (30 days) of both sexes in the Morris water maze. Different groups were trained in spatial working (WM) or reference memory (RM) tasks, respectively. The corresponding naïve groups swam for the same amount of time as the trained groups but without the escape platform. Control groups were added that had not been manipulated in any way. No sex-related differences were detected in the working memory task although males exhibited better reference memory than females. Cytochrome oxidase (CO) activity, an endogenous metabolic marker for neuronal activity, was measured in all the groups. CO activity increased significantly in both MB nuclei of male and female rats only in the spatial working memory group. In addition, high CO activity in the lateral nucleus of the MB was linearly correlated with lower escape latencies in both sexes after training in the working memory task. No CO activity changes were found in the basolateral amygdala (BL) in any of the experimental groups. This nucleus was used as a control brain region because of its participation in emotional behavior. The results suggest a specific role of the MB nuclei in spatial working memory in both sexes.

[1]  A Poremba,et al.  Classical conditioning modifies cytochrome oxidase activity in the auditory system , 1998, The European journal of neuroscience.

[2]  Helmut Hildebrandt,et al.  Are Some Memory Deficits Unique to Lesions of the Mammillary Bodies? , 2001, Journal of clinical and experimental neuropsychology.

[3]  L. Santín,et al.  c-Fos expression in supramammillary and medial mammillary nuclei following spatial reference and working memory tasks , 2003, Physiology & Behavior.

[4]  L Weiskrantz,et al.  Memory disorder in Korsakoff's psychosis: a neuropathological and neuropsychological investigation of two cases. , 1979, Brain : a journal of neurology.

[5]  A. Chiba,et al.  Spatial learning in male and female Long-Evans rats. , 1995, Behavioral neuroscience.

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

[7]  F. Gonzalez-Lima,et al.  Cytochrome oxidase activity in the auditory system of the mouse: A qualitative and quantitative histochemical study , 1994, Neuroscience.

[8]  Douglas W. Barrett,et al.  Metabolic mapping of brain regions associated with behavioral extinction in preweanling rats , 2001, Brain Research.

[9]  J. Cimadevilla,et al.  Sex-related differences in spatial learning during the early postnatal development of the rat , 1999, Behavioural Processes.

[10]  D. Touretzky,et al.  Modeling attractor deformation in the rodent head-direction system. , 2000, Journal of neurophysiology.

[11]  M. Wong-Riley Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry , 1979, Brain Research.

[12]  L. Santín,et al.  Effects of mammillary body lesions on spatial reference and working memory tasks , 1999, Behavioural Brain Research.

[13]  D. Stein,et al.  Gender differences in Morris water maze performance depend on task parameters , 1999, Physiology & Behavior.

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

[15]  R. Roof,et al.  Testosterone improves maze performance and induces development of a male hippocampus in females , 1992, Brain Research.

[16]  M. Wong-Riley Cytochrome oxidase: an endogenous metabolic marker for neuronal activity , 1989, Trends in Neurosciences.

[17]  A key role of the mammillary body in mediation of the antianxiety action of zopiclone, a cyclopyrrolone derivative. , 1989, Japanese journal of pharmacology.

[18]  J. Sergeant,et al.  A quantitative cytochrome oxidase mapping study, cross-regional and neurobehavioural correlations in the anterior forebrain of an animal model of Attention Deficit Hyperactivity Disorder , 1998, Behavioural Brain Research.

[19]  J. Mcculloch,et al.  The effect of diazepam upon local cerebral glucose use in the conscious rat , 1986, Neuroscience.

[20]  M. Petrides,et al.  Memory for Places and the Region of the Mamillary Bodies in Rats , 1990, The European journal of neuroscience.

[21]  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.

[22]  V. Denenberg,et al.  In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze , 2000, Physiology & Behavior.

[23]  J. Gray,et al.  Précis of The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system , 1982, Behavioral and Brain Sciences.

[24]  R. Roof,et al.  Neonatal exogenous testosterone modifies sex difference in radial arm and morris water maze performance in prepubescent and adult rats , 1993, Behavioural Brain Research.

[25]  E. Irle,et al.  Single and combined lesions of the cat's thalamic mediodorsal nucleus and the mamillary bodies lead to severe deficits in the acquisition of an alternation task , 1982, Behavioural Brain Research.

[26]  F. Gonzalez-Lima,et al.  Water maze training in aged rats: effects on brain metabolic capacity and behavior , 2002, Brain Research.

[27]  Dirk Jones,et al.  Quantitative mapping of cytovhrome oxidase activity in the central auditory system of the gerbil: a study with calibrated activity standards and metal-intensified histochemistry , 1994, Brain Research.

[28]  I. Kirk,et al.  Evidence for Differential Control of Posterior Hypothalamic, Supramammillary, and Medial Mammillary Theta-Related Cellular Discharge by Ascending and Descending Pathways , 1996, The Journal of Neuroscience.

[29]  H. Markowitsch Diencephalic amnesia: a reorientation towards tracts? , 1988, Brain Research Reviews.

[30]  M. Petrides,et al.  Memory Impairments Following Lesions to the Mammillary Region of the Rat , 1993, The European journal of neuroscience.

[31]  J. O’Keefe,et al.  Phase relationship between hippocampal place units and the EEG theta rhythm , 1993, Hippocampus.

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

[33]  A. Fenton,et al.  Continuous place avoidance task reveals differences in spatial navigation in male and female rats , 2000, Behavioural Brain Research.

[34]  G. Dohanich,et al.  Effects of Ovarian Hormones and Environment on Radial Maze and Water Maze Performance of Female Rats , 1999, Physiology & Behavior.

[35]  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.

[36]  M. W. Brown,et al.  Episodic memory, amnesia, and the hippocampal–anterior thalamic axis , 1999, Behavioral and Brain Sciences.

[37]  T. Sharp,et al.  Induction of c-Fos expression in specific areas of the fear circuitry in rat forebrain by anxiogenic drugs , 2003, Biological Psychiatry.

[38]  Y. Tanaka,et al.  Amnesia Following Damage to the Mammillary Bodies , 1997, Neurology.

[39]  M. Mishkin,et al.  Mamillary-body lesions and visual recognition in monkeys , 2004, Experimental Brain Research.

[40]  J. Juraska,et al.  Differential rearing experience, gender, and radial maze performance. , 1984, Developmental psychobiology.

[41]  R. Vertes,et al.  Characterization of neurons of the supramammillary nucleus and mammillary body that discharge rhythmically with the hippocampal theta rhythm in the rat , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  R D Adams,et al.  The Wernicke-Korsakoff syndrome. A clinical and pathological study of 245 patients, 82 with post-mortem examinations. , 1971, Contemporary neurology series.

[43]  J. Stewart,et al.  Effects of neonatal androgens on open-field behavior and maze learning in the prepubescent and adult rat , 1975, Physiology & Behavior.

[44]  N. Neave,et al.  Evidence for the Involvement of the Mammillary Bodies and Cingulum Bundle in Allocentric Spatial Processing by Rats , 1997, The European journal of neuroscience.

[45]  M. Petrides,et al.  Selectivity of the spatial learning deficit after lesions of the mammillary region in rats , 2000, Hippocampus.

[46]  B H Bland,et al.  Discharge patterns of hippocampal theta-related cells in the caudal diencephalon of the urethan-anesthetized rat. , 1995, Journal of neurophysiology.

[47]  B. J. Yates,et al.  Does the vestibular system contribute to head direction cell activity in the rat? , 2002, Physiology & Behavior.

[48]  D J Beracochea,et al.  Effects of mammillary body and mediodorsal thalamic lesions on elevated plus maze exploration. , 1991, Neuroreport.

[49]  V. Braithwaite,et al.  Spatial working memory in rats: no differences between the sexes , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[50]  J. Aggleton,et al.  Evidence of a Spatial Encoding Deficit in Rats with Lesions of the Mammillary Bodies or Mammillothalamic Tract , 2003, The Journal of Neuroscience.

[51]  R. Llinás,et al.  Electrophysiology of the mammillary complex in vitro. II. Medial mammillary neurons. , 1992, Journal of neurophysiology.

[52]  Michael Davis,et al.  Neurotransmission in the rat amygdala related to fear and anxiety , 1994, Trends in Neurosciences.

[53]  E. Greene,et al.  Behavioral role of the mammillary efferent system , 1978, Brain Research Bulletin.

[54]  M. Petrides,et al.  MEMORY AND THE REGION OF THE MAMMILLARY BODIES , 1998, Progress in Neurobiology.

[55]  L R Squire,et al.  Amnesia in monkeys after lesions of the mediodorsal nucleus of the thalamus , 1985, Annals of neurology.

[56]  R. Vertes Brainstem Modulation of the Hippocampus , 1986 .

[57]  Y. Gomita,et al.  The mammillary body is a potential site of antianxiety action of benzodiazepines , 1982, Brain Research.

[58]  M. Kopelman The Korsakoff Syndrome , 1995, British Journal of Psychiatry.

[59]  N. V. Poll,et al.  Absence of behavioral differences between male and female rats in different radial-maze procedures , 1987, Physiology & Behavior.

[60]  J. Nesbit,et al.  The effect of early visual experience on spatial maze learning in rats. , 1981, Developmental psychobiology.

[61]  R. Vertes,et al.  Phase relations of rhythmic neuronal firing in the supramammillary nucleus and mammillary body to the hippocampal theta activity in urethane anesthetized rats , 1997, Hippocampus.

[62]  J. Taube,et al.  Firing Properties of Rat Lateral Mammillary Single Units: Head Direction, Head Pitch, and Angular Head Velocity , 1998, The Journal of Neuroscience.

[63]  M. Sarter,et al.  2-[3H]deoxyglucose uptake patterns in rats exploring a six-arm radial tunnel maze: differences between experienced and nonexperienced rats. , 1989, Behavioral neuroscience.

[64]  D. Béracochéa,et al.  Effects of mammillary bodies and mediodorsal thalamic lesions on the acquisition and retention of a learning set in mice: paradoxical effect of the intersession interval , 1995, Behavioural Brain Research.

[65]  B. Bontempi,et al.  Differential Temporal Evolution of Post‐Training Changes in Regional Brain Glucose Metabolism Induced by Repeated Spatial Discrimination Training in Mice: Visualization of the Memory Consolidation Process? , 1996, The European journal of neuroscience.

[66]  Andrew R. Mayes,et al.  Location of Lesions in Korsakoff's Syndrome: Neuropsychological and Neuropathological Data on Two Patients , 1988, Cortex.

[67]  D. Olton,et al.  Spatial memory and hippocampal function , 1979, Neuropsychologia.

[68]  F. Gonzalez-Lima Cytochrome Oxidase in Neuronal Metabolism and Alzheimer’s Disease , 2013, Springer US.

[69]  P. Goldman-Rakic,et al.  Enhancement of Metabolic Activity in the Diencephalon of Monkeys Performing Working Memory Task: A 2-Deoxyglucose Study in Behaving Rhesus Monkeys , 1990, Journal of Cognitive Neuroscience.

[70]  Warren H. Meck,et al.  Organizational effects of early gonadal secretions on sexual differentiation in spatial memory. , 1990, Behavioral Neuroscience.