Withdrawal from continuous amphetamine administration abolishes latent inhibition but leaves prepulse inhibition intact

Rationale: Schizophrenia has been associated with dysregulation of dopamine (DA) transmission and impairment in a number of experimental tasks, including sensorimotor gating assessed using prepulse inhibition (PPI) and selective attention assessed using latent inhibition (LI). We have demonstrated in previous studies that after withdrawal from escalating (ESC) dosages of amphetamine (AMPH), animals exhibited disruption of LI but no alteration of PPI. Moreover, these animals always showed behavioural sensitization to an AMPH challenge. Objective: In this study, we were interested in testing whether a different administration schedule would elicit disruption of both LI and PPI. Methods: Animals were treated with continuous AMPH release (via osmotic mini-pumps at a dosage of 10mg kg−1 day−1 for 7 days) and tested for their performance in L and PPI during withdrawal in a drug free state. Rats received AMPH treatment during the induction phase in their home cages or in the activity chambers. Following withdrawal, the expression of behavioural sensitization to an AMPH challenge was tested in both cases in the activity chambers. Results: Animals pretreated with AMPH from both groups did not exhibit behavioural sensitization. Withdrawal from continuous administration induced LI attenuation with no effect on PPI. Conclusions: These findings are similar to what was previously found with respect to an ESC AMPH regime. The only difference between the schedules was that the ESC AMPH schedule led to behavioural sensitization whereas the continuous AMPH did not. It is suggested that the expression of sensitization may not be a prerequisite for observed LI disruptio

Withdrawal from continuous amphetamine administration abolishes latent inhibition but leaves prepulse inhibition intact

ISSN:0033-3158ISSN:1432-207

Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast is widely used for probing brain activity, but its relationship to underlying neural activity remains elusive. Here, we combined fMRI with fiber-optic recordings of fluorescent calcium indicator signals to investigate this relationship in rat somatosensory cortex. Electrical forepaw stimulation (1-10 Hz) evoked fast calcium signals of neuronal origin that showed frequency-dependent adaptation. Additionally, slower calcium signals occurred in astrocyte networks, as verified by astrocyte-specific staining and two-photon microscopy. Without apparent glia activation, we could predict BOLD responses well from simultaneously recorded fiber-optic signals, assuming an impulse response function and taking into account neuronal adaptation. In cases with glia activation, we uncovered additional prolonged BOLD signal components. Our findings highlight the complexity of fMRI BOLD signals, involving both neuronal and glial activity. Combined fMRI and fiber-optic recordings should help to clarify cellular mechanisms underlying BOLD signals

FMRI in mice: functional phenotyping of transgenic mouse lines based on hemodynamic readouts

Considering the increasing number of genetically engineered mouse models of human neurological or psychiatric pathologies there is a rising demand of tools for structural and functional phenotyping. Methods that allow non-invasive assessment of brain function such as functional MRI (fMRI) are highly attractive in this context. This review aims to make the reader aware of the potential of functional MRI (fMRI) in brain activation studies in mice with the focus on experimental aspects of hemodynamic-based readouts such as BOLD (blood-oxygen level dependent contrast) or CBV (cerebral blood volume)-based fMRI, and there application to mouse models of CNS disorders. Due to the non-invasiveness nature of MRI functional consequences of disease progression can be investigated in longitudinal studies providing information on disease evolution in the individual that can be combined with more traditional pharmacological readouts (i.e. behavioural assessments). FMRI studies investigating transgenic models of brain disorders characterizing the disease phenotype and assessing the efficacy of a therapeutic intervention are therefore warranted and it is anticipated that the fi eld will rapidly grow

Rewiring of hindlimb corticospinal neurons after spinal cord injury

Little is known about the functional role of axotomized cortical neurons that survive spinal cord injury. Large thoracic spinal cord injuries in adult rats result in impairments of hindlimb function. Using retrograde tracers, we found that axotomized corticospinal axons from the hindlimb sensorimotor cortex sprouted in the cervical spinal cord. Mapping of these neurons revealed the emergence of a new forelimb corticospinal projection from the rostral part of the former hindlimb cortex. Voltage-sensitive dye (VSD) imaging and blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) revealed a stable expansion of the forelimb sensory map, covering in particular the former hindlimb cortex containing the rewired neurons. Therefore, axotomised hindlimb corticospinal neurons can be incorporated into the sensorimotor circuits of the unaffected forelimb