Microglia are phagocytic cells that infiltrate the brain during development and have a role in the elimination of synapses during brain maturation. Changes in microglial morphology and gene expression have been associated with neurodevelopmental disorders. However, it remains unknown whether these changes are a primary cause or a secondary consequence of neuronal deficits. Here we tested whether a primary deficit in microglia was sufficient to induce some autism-related behavioral and functional connectivity deficits. Mice lacking the chemokine receptor Cx3cr1 exhibit a transient reduction of microglia during the early postnatal period and a consequent deficit in synaptic pruning. We show that deficient synaptic pruning is associated with weak synaptic transmission, decreased functional brain connectivity, deficits in social interaction and increased repetitive-behavior phenotypes that have been previously associated with autism and other neurodevelopmental and neuropsychiatric disorders. These findings open the possibility that disruptions in microglia-mediated synaptic pruning could contribute to neurodevelopmental and neuropsychiatric disorders.

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Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior

Distributed BOLD and CBV-weighted resting-state networks in the mouse brain

Large-scale functional connectivity networks in the rodent brain.

A Neural Switch for Active and Passive Fear

Functional connectivity hubs of the mouse brain.

A robust experimental protocol for pharmacological fMRI in rats and mice

We sought to evaluate a new protocol designed to maintain long-term, nonrecovery, surgical anesthesia in Sprague-Dawley rats. In the first phase, two groups of rats were anesthetized with two different dose combinations of Domitor (medetomidine) and Zoletil 100 (tiletamine-zolazepam) to investigate their efficacy in induction of anesthesia. One combination comprised Domitor at 35 microg/kg and Zoletil 100 at 40 mg/kg, whereas the other comprised Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg. Both combinations effectively induced deep anesthesia and caused no mortality, but the duration of anesthesia differed statistically. In the second phase, we induced anesthesia with both Domitor-Zoletil 100 dose combinations then investigated the possibility of maintaining anesthesia for 5 h by administering Euthatal (pentobarbitone) intra-arterially at 10 mg/kg hourly. Depth of anesthesia, mortality, physiological parameters, blood gas analysis, hematology, clinical chemistry, and postmortem histopathology were recorded. Euthatal provided stable long-term anesthesia with both dose combinations of Domitor-Zoletil 100. Seven of 8 (88%) animals anesthetized with Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg successfully were maintained under deep anesthesia for 5 h. Higher mortality (36% versus 12%) occurred in group of animals treated with Domitor at 35 microg/kg and Zoletil 100 at 40 mg/kg. This difference may be linked to dose-related respiratory depression, as alterations of arterial gas levels were noted. Our findings suggest that, when long-term nonrecovery anesthesia is required, doses of 50 microg/kg Domitor and 20 mg/kg Zoletil 100 are preferable when given with Euthatal to maintain physiological conditions in animals.

Livia Ferrari

Papers

A robust experimental protocol for pharmacological fMRI in rats and mice

Evaluation of two combinations of Domitor, Zoletil 100, and Euthatal to obtain long-term nonrecovery anesthesia in Sprague-Dawley rats.

Brain penetration of local anaesthetics in the rat: Implications for experimental neuroscience.