Prepulse Inhibition Deficits in GAD65 Knockout Mice and the Effect of Antipsychotic Treatment

Heldt, Scott A.; Green, Amanda; Ressler, Kerry J.

doi:10.1038/sj.npp.1300468

Cited by 58 publications

(40 citation statements)

References 78 publications

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“…A deficiency or even the absence of PPI of ASR was observed in mice with GABA A receptor ␥2 subunits removed from the PVpositive neurons [16], in GAD65 knockout mice [12] and in dystonic hamsters [11].…”

Section: Discussionmentioning

confidence: 99%

The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice

Popelář

Rybalko

Burianová

et al. 2013

Neuroscience Letters

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h i g h l i g h t s• PV−/− mice had smaller ASR amplitudes in response to relatively weak startling stimuli (80-90 dB SPL) in comparison with PV+/+ mice.• PPI of the ASR in PV−/− mice was less effective than in PV+/+ mice.• Mean ABR audiograms were found to be similar in both genotypes.The strength of the acoustic startle response (ASR) to short bursts of broadband noise or tone pips (4, 8 and 16 kHz) and the prepulse inhibition (PPI) of the ASR elicited by prepulse tones (4, 8 and 16 kHz) were measured in parvalbumin-deficient (PV−/−) mice and in age-matched PV+/+ mice as controls. Hearing thresholds as determined from recordings of auditory brainstem responses were found to be similar in both genotypes. The ASRs to broadband noise and tones of low and middle frequencies were stronger than the ASRs in response to high-frequency tones in both groups. In PV−/− mice, we observed smaller ASR amplitudes in response to relatively weak startling stimuli (80-90 dB sound pressure level (SPL)) of either broadband noise or 8-kHz tones compared to those recorded in PV+/+ mice. For these startling stimuli, PV−/− mice had higher ASR thresholds and longer ASR latencies. PPI of the ASR in PV−/− mice was less effective than in PV+/+ mice, for all tested prepulse frequencies (4, 8 or 16 kHz) at 70 dB SPL. Our findings demonstrate no effect of PV deficiency on hearing thresholds in PV−/− mice. However, the frequency-specific differences in the ASR and the significant reduction of PPI of ASR likely reflect specific changes of neuronal circuits, mainly inhibitory, in the auditory centers in PV-deficient mice..

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Section: Discussionmentioning

confidence: 99%

The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice

Popelář

Rybalko

Burianová

et al. 2013

Neuroscience Letters

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“…Pre-pulse inhibition (PPI) testing is described in detail in Heldt et al (2004). Briefly, 12 behaviorally-naive mice (6 per genotype) were placed in startle testing/training chambers (see above), and presented with either startle stimuli alone (110 dB, 50 ms) or startle stimuli preceded by white noise pre-pulses (20 ms) of 2, 4, 8, 10, or 12 dB above a 63 dB white noise background (i.e., 65, 67, 71, 73, or 75dB) with a fixed interval (100 ms) between onsets of the pre-pulse and startle stimulus.…”

Section: Prepulse Inhibitionmentioning

confidence: 99%

Learning and memory deficits in mice lacking protease activated receptor-1

Almonte

Hamill

Chhatwal

et al. 2007

Neurobiology of Learning and Memory

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The roles of serine proteases and protease activated receptors have been extensively studied in coagulation, wound healing, inflammation, and neurodegeneration. More recently, serine proteases have been suggested to influence synaptic plasticity. In this context, we examined the role of protease activated receptor 1 (PAR1), which is activated following proteolytic cleavage by thrombin and plasmin, in emotionally-motivated learning. We were particularly interested in PAR1 because its activation enhances the function of NMDA receptors, which are required for some forms of synaptic plasticity. We examined several baseline behavioral measures, including locomotor activity, expression of anxiety-like behavior, motor task acquisition, nociceptive responses, and startle responses in C57Bl/6 mice in which the PAR1 receptor has been genetically deleted. In addition, we evaluated learning and memory in these mice using two memory tasks, passive avoidance and cued fear-conditioning. Whereas locomotion, pain response, startle, and measures of baseline anxiety were largely unaffected by PAR1 removal, PAR1−/− animals showed significant deficits in a passive avoidance task and in cued fear conditioning. These data suggest that PAR1 may play an important role in emotionally-motivated learning.

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“…To examine the effects of clozapine on the group differences, all animals were tested for PPI in the presence of clozapine (6 mg/kg) or vehicle with a random crossover experimental design using a within-groups comparison for drug effect. As with other studies which have employed this design, a 3 day drug washout period was given between tests (e.g., Johansson et al, 1995;Heldt et al, 2004). Of the initial 42 mice, approximately one half were subsequently given open-field testing after an additional 1 week drug washout period (habenula lesioned, n = 13; sham lesioned, n = 13).…”

Section: Animals and Experimental Designmentioning

confidence: 99%

“…with 200 μl of drug or vehicle 30 min before behavioral testing. The drug concentrations were chosen on the basis of previous studies of doses required to obtain behavioral effects in mice and rats (e.g., Zhang et al, 1998;Dirks et al, 2003;Heldt et al, 2004).…”

Section: Drugsmentioning

confidence: 99%

Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion

Heldt

Ressler

2006

Brain Research

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The habenula complex modulates the a ctivity of dopamine and serotonin systems in the brain. An important question remains whether there is a link between habenula dysfunction and monoaminerelated disorders, such as schizophrenia. In this study, we describe an interaction between habenula lesions and stress that produces long-lasting effects on behavior. Mice received control lesions or bilateral electrolytic lesions of the habenula and were tested for fear-potentiated startle and freezing measures of conditioned fear. They w ere also tested for prepulse inhibition (PPI) and locomotor activity in the presence or absence of a dopaminergic agonist (apomorphine) or an atypical antipsychotic with mixed dopamine/serotonin antagonist properties (clozapine). There were no detectable effects of habenula lesions on fear conditioning and no effects on PPI in the absence o f stress. However, following conditioned fear stress, habenula-lesioned animals showed decreased PPI which normalized with clozapine. Lesioned animals also showed diminished activity at baseline, with hyperlocomotion following apomorphine. These data support the hypothesis that the habenula may be normally involved in stress-dependent regulation of monoamine systems.

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Prepulse Inhibition Deficits in GAD65 Knockout Mice and the Effect of Antipsychotic Treatment

Cited by 58 publications

References 78 publications

The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice

The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice

Learning and memory deficits in mice lacking protease activated receptor-1

Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion

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