Emotional disorders in adult mice heterozygous for the transcription factor Phox2b.

Phox2b is an essential transcription factor for the development of the autonomic nervous system. Mice carrying one invalidated Phox2b allele (Phox2b(+/-)) show mild autonomic disorders including sleep apneas, and impairments in chemosensitivity and thermoregulation that recover within 10days of postnatal age. Because Phox2b is not expressed above the pons nor in the cerebellum, this mutation is not expected to affect brain development and cognitive functioning directly.

Haploinsufficiency of VGluT1 but not VGluT2 impairs extinction of spatial preference and response suppression.

The excitatory neurotransmitter l-glutamate is transported into synaptic vesicles by vesicular glutamate transporters (VGluTs) to transmit glutamatergic signals. Changes in their expression have been linked to various brain disorders including schizophrenia, Parkinson's, and Alzheimer's disease. Deleting either the VGluT1 or VGluT2 gene leads to profound developmental and neurological complications and early death, but mice heterozygous for VGluT1 or VGluT2 are viable and thrive.

Behavioural alterations relevant to developmental brain disorders in mice with neonatally induced ventral hippocampal lesions.

Neonatal lesioning of the ventral hippocampus (vHc) in rats has served as a useful heuristic animal model to elucidate neurodevelopmental mechanisms of schizophrenia (SCZ). In the current study we have established that this procedure can be applied to model SCZ symptomatology in mice. Neonatal mice (postnatal day 6) were anaesthetised by hypothermia and electrolytic lesions of the vHc were induced.

Vglut2 haploinsufficiency enhances behavioral sensitivity to MK-801 and amphetamine in mice.

Recently developed mouse models have implicated the vesicular glutamate transporter 2 (VGLUT2) in psychostimulant-induced hyperactivity, a behavioral assay that is often applied to evaluate mouse behavior related to positive schizophrenia (SCZ) symptomatology. In present research, we wanted to evaluate further the role of subtle VGLUT2 impairment as a factor underlying SCZ symptomatology. To this end, we evaluated Vglut2 haploinsufficient (Vglut2⁺/⁻) mice and their wildtype littermates in a test battery assessing behaviors related to positive, negative and cognitive SCZ symptom domains.

Nocturnal hyperactivity, increased social novelty preference and delayed extinction of fear responses in post-weaning socially isolated mice.

When rodents are reared in isolation from young age onwards, they manifest a number of behavioural alterations in adulthood. Since some of these alterations resemble symptoms of psychiatric disorders, the post-weaning social isolation (ISO) manipulation is often applied to create rodent models of these disorders. In rats, ISO effects have been thoroughly characterised, but in mice they are less well documented.

Serotonin transporter binding in the hypothalamus correlates negatively with tonic heat pain ratings in healthy subjects: a [11C]DASB PET study.

There is a large body of evidence that the serotonergic system plays an important role in the transmission and regulation of pain. Here we used positron emission tomography (PET) with the serotonin transporter (SERT) tracer [(11)C]DASB to study the relationship between SERT binding in the brain and responses to noxious heat stimulation in a group of 21 young healthy volunteers. Responses to noxious heat stimuli were assessed in a separate psychophysical experiment and included measurements of pain threshold, pain tolerance, and responses to phasic noxious heat stimuli and to a long lasting (7-minute) tonic noxious heat stimulus.

No evidence for generalized increased postoperative responsiveness to pain: a combined behavioral and serial functional magnetic resonance imaging study.

Background: Although it is generally accepted that increased pain responsiveness and central sensitization develop after major tissue injury, this claim has not been tested using brain imaging methods in a clinical pain setting. We tested this hypothesis using a postoperative pain model, in conjunction with serial functional magnetic resonance imaging (fMRI).

Methods: We studied brain and subjective pain responses to innocuous and noxious heat in seven patients before and after total knee arthroplasty.

A PET [18F]altanserin study of 5-HT2A receptor binding in the human brain and responses to painful heat stimulation.

There is a large body of evidence that serotonin [5-hydroxytryptamine (5-HT)] plays an important role in the transmission and regulation of pain. Here we used positron emission tomography (PET) to study the relationship between baseline 5-HT(2A) binding in the brain and responses to noxious heat stimulation in a group of young healthy volunteers. Twenty-one healthy subjects underwent PET scanning with the 5-HT(2A) antagonist, [(18)F]altanserin.

Characterization of a novel model of tonic heat pain stimulation in healthy volunteers.

The vast majority of the experimental pain studies have used acute, phasic heat stimuli to investigate the neurobiological mechanisms of pain. However, the validity of these models for understanding clinical forms of pain is questionable. We here describe the characteristics of a model of prolonged tonic heat pain stimulation and compared the responses on this test with other measures of pain.