Individual difference in prepulse inhibition does not predict spatial learning and memory performance in C57BL/6 mice

The startle reflex to an intense acoustic pulse stimulus is attenuated if the pulse stimulus is shortly preceded by a weak non-startling prepulse stimulus. This attenuation of the startle reflex represents a form of pre-attentional sensory gating known as prepulse inhibition (PPI). Although PPI does not require learning, its expression is regulated by higher cognitive processes. PPI deficits have been detected in several psychiatric conditions including schizophrenia where they co-exist with cognitive deficits. A potential link between PPI expression and cognitive performance has therefore been suggested such that poor PPI may predict, or may be mechanistically linked to, overt cognitive impairments. A positive relationship between PPI and strategy formation, planning efficiency, and execution speed has been observed in healthy humans. However, parallel studies in healthy animals are rare. It thus remains unclear what cognitive domains may be associated with, or orthogonal to, sensory gating in the form of PPI in healthy animals. The present study evaluated a potential link between the magnitude of PPI and spatial memory performance by comparing two subgroups of animals differing substantially in baseline PPI expression (low-PPI vs high-PPI) within a homogenous cohort of 100 male adult C57BL/6 mice. Assessment of spatial reference memory in the Morris water maze and spatial recognition memory in the Y-maze failed to reveal any difference between low-PPI and high-PPI subjects. These negative findings contrast with our previous reports that individual difference in PPI correlated with sustained attention and working memory performance in C57BL/6 mice.

[1]  J. Feldon,et al.  Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice , 2009, Psychopharmacology.

[2]  H. Hoffman,et al.  ACOUSTIC VARIABLES IN THE MODIFICATION OF STARTLE REACTION IN THE RAT. , 1965, Journal of comparative and physiological psychology.

[3]  G. Waldemar,et al.  Prepulse inhibition in patients with Alzheimer’s disease , 2004, Neurobiology of Aging.

[4]  J. Hagan,et al.  Predicting drug efficacy for cognitive deficits in schizophrenia. , 2005, Schizophrenia bulletin.

[5]  M. Geyer,et al.  The relationship of age to prepulse inhibition and habituation of the acoustic startle response , 2003, Biological Psychology.

[6]  Robert L Levin,et al.  Food and Drug Administration commentary on methodological issues in negative symptom trials. , 2011, Schizophrenia bulletin.

[7]  F. Vollenweider,et al.  On the influence of baseline startle reactivity on the indexation of prepulse inhibition. , 2008, Behavioral neuroscience.

[8]  M. Martin-Iverson,et al.  Disturbed prepulse inhibition in patients with schizophrenia is consequential to dysfunction of selective attention. , 2010, Psychophysiology.

[9]  P. Dudchenko An overview of the tasks used to test working memory in rodents , 2004, Neuroscience & Biobehavioral Reviews.

[10]  J. Feldon,et al.  Limited impact of social isolation on Alzheimer-like symptoms in a triple transgenic mouse model. , 2009, Behavioral neuroscience.

[11]  B. Yee,et al.  Reversal of scopolamine-induced disruption of prepulse inhibition by clozapine in mice , 2012, Pharmacology Biochemistry and Behavior.

[12]  Joseph E LeDoux,et al.  Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. , 1992, Behavioral neuroscience.

[13]  K. Nuechterlein,et al.  Attention and schizophrenia: impaired modulation of the startle reflex. , 1993, Journal of abnormal psychology.

[14]  J. Feldon,et al.  Deletion of glycine transporter 1 (GlyT1) in forebrain neurons facilitates reversal learning: enhanced cognitive adaptability? , 2009, Behavioral neuroscience.

[15]  S. Giakoumaki,et al.  Relationship of prepulse inhibition of the startle reflex to attentional and executive mechanisms in man. , 2005, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[16]  N. Swerdlow,et al.  Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges , 2001, Psychopharmacology.

[17]  M. Geyer Are cross-species measures of sensorimotor gating useful for the discovery of procognitive cotreatments for schizophrenia? , 2006, Dialogues in clinical neuroscience.

[18]  David A. Smith,et al.  Test-retest reliability of prepulse inhibition of the acoustic startle response , 1993, Biological Psychiatry.

[19]  S. Frangou,et al.  The level of prepulse inhibition in healthy individuals may index cortical modulation of early information processing , 2006, Brain Research.

[20]  J. Feldon,et al.  Sensorimotor gating and vigilance-dependent choice accuracy: A within-subject correlative analysis in wild-type C57BL/6 mice , 2011, Behavioural Brain Research.

[21]  N. Sato,et al.  Prepulse inhibition of acoustic startle response in mild cognitive impairment and mild dementia of Alzheimer type , 2006, Psychiatry and clinical neurosciences.

[22]  M. Geyer The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps? , 2006, Neurotoxicity Research.

[23]  S. Frangou,et al.  Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males , 2006, Neuropsychologia.

[24]  Joyce Sprock,et al.  Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function. , 2006, Archives of general psychiatry.

[25]  M. Geyer,et al.  Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels , 2008, Neuropsychopharmacology.

[26]  J. Rawlins,et al.  Deletion of glutamate receptor-A (GluR-A) AMPA receptor subunits impairs one-trial spatial memory. , 2007, Behavioral neuroscience.

[27]  G. Handelmann,et al.  Hippocampus, space, and memory , 1979 .

[28]  D. Feifel Individual differences in prepulse inhibition of startle as a measure of individual dopamine function. , 1999, Behavioral neuroscience.

[29]  V. V. Dolgov,et al.  GABAA receptors containing the α5 subunit mediate the trace effect in aversive and appetitive conditioning and extinction of conditioned fear , 2004, The European journal of neuroscience.

[30]  B. Yee,et al.  Baseline prepulse inhibition expression predicts the propensity of developing sensitization to the motor stimulant effects of amphetamine in C57BL/6 mice , 2012, Psychopharmacology.

[31]  J. Feldon,et al.  Prepulse inhibition predicts working memory performance whilst startle habituation predicts spatial reference memory retention in C57BL/6 mice , 2013, Behavioural Brain Research.

[32]  W. K. Honig,et al.  Cognitive Processes in Animal Behavior , 1979 .

[33]  A. Baddeley Working memory: theories, models, and controversies. , 2012, Annual review of psychology.

[34]  David J. Sanderson,et al.  NMDA Receptor Subunit NR2A Is Required for Rapidly Acquired Spatial Working Memory But Not Incremental Spatial Reference Memory , 2008, The Journal of Neuroscience.

[35]  R. Mott,et al.  Applying mouse complex-trait resources to behavioural genetics , 2008, Nature.

[36]  M. Geyer,et al.  The effects of sertindole on sensory gating, sensorimotor gating, and cognition in healthy volunteers , 2011, Journal of psychopharmacology.

[37]  David Hemsley,et al.  Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls , 1998, Journal of psychopharmacology.

[38]  J. Feldon,et al.  The expression of prepulse inhibition of the acoustic startle reflex as a function of three pulse stimulus intensities, three prepulse stimulus intensities, and three levels of startle responsiveness in C57BL6/J mice , 2005, Behavioural Brain Research.

[39]  M. Martin-Iverson,et al.  Relationships between prepulse inhibition and cognition are mediated by attentional processes , 2009, Behavioural Brain Research.

[40]  T. Robbins,et al.  Complementary roles for the amygdala and hippocampus in aversive conditioning to explicit and contextual cues , 1991, Neuroscience.

[41]  Robert L Levin,et al.  Food and Drug Administration perspective on negative symptoms in schizophrenia as a target for a drug treatment claim. , 2006, Schizophrenia bulletin.

[42]  J. Feldon,et al.  The Effects of Dizocilpine and Phencyclidine on Prepulse Inhibition of the Acoustic Startle Reflex and on Prepulse-Elicited Reactivity in C57BL6 Mice , 2004, Neuropsychopharmacology.

[43]  M. Geyer,et al.  Mouse genetic models for prepulse inhibition: an early review , 2002, Molecular Psychiatry.

[44]  N. Swerdlow,et al.  Measurement of Startle Response, Prepulse Inhibition, and Habituation , 1998, Current protocols in neuroscience.

[45]  J. Rawlins,et al.  Regional dissociations within the hippocampus—memory and anxiety , 2004, Neuroscience & Biobehavioral Reviews.

[46]  Jared W. Young,et al.  Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. , 2009, Pharmacology & therapeutics.

[47]  J. Feldon,et al.  The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex , 2008, Psychopharmacology.

[48]  S. Hackley,et al.  The more or less startling effects of weak prestimulation - Revisted : Prepulse modulation of multicomponent blink reflexes , 1997 .

[49]  Franz X. Vollenweider,et al.  Stability of the acoustic startle reflex, prepulse inhibition, and habituation in schizophrenia , 2002, Schizophrenia Research.

[50]  B. Campbell,et al.  Attention and information Processing in infants and Adults : Perspectives From Human and Animal Research , 2014 .