Reduced Inhibitory Inputs On Basolateral Amygdala Principal Neurons Following Long-Term Alcohol Consumption

Recent studies have shown that manipulating basolateral amygdala (BLA) activity can affect alcohol consumption, particularly following chronic and/or long-term intake. Although the mechanisms underlying these effects remain unclear, the BLA is highly sensitive to emotional stimuli including stress and anxiety. Negative emotional states facilitate alcohol craving and relapse in patients with alcohol use disorders. Consequently, the aim of this study was to determine the effect of long-term (10 weeks) alcohol drinking on synaptic activity in BLA principal neurons. We utilized an intermittent drinking paradigm in rats, which facilitated escalating, binge-like alcohol intake over the 10 week drinking period. We then recorded spontaneous excitatory and inhibitory postsynaptic currents of BLA principal neurons from long-term alcohol drinking rats and aged-matched water drinking controls. Excitatory postsynaptic current properties from long-term alcohol drinking rats were unchanged compared to those from age-matched water drinking controls. Conversely, we observed significant reductions of inhibitory postsynaptic current amplitude and frequency in long-term ethanol drinking rats compared to age-matched water drinking controls. These results highlight substantive decreases in basal inhibitory synaptic activity of BLA principal neurons following long-term alcohol consumption. A loss of inhibitory control in the BLA could explain the high incidence of compulsive drinking and stress- or anxiety-induced relapse in patients with alcohol use disorders.</p

Quantitative, high sensitivity, high resolution, nuclear microprobe imaging of fluids, melts and minerals

Samples of fluids and melts trapped and preserved as inclusions in growing minerals or healed fractures provide unique windows on a range of geological processes from mantle melting and metasomatism through to economic ore formation and remobilization. Recent advances in nuclear microprobe (NMP) technology at the CSIRO provide powerful tools for the study of these inclusions and associated mineral assemblages. These tools include a new NMP designed for high resolution and high sensitivity, PIXE analytical methods for quantitative imaging and analysis, and simultaneous PIGE imaging. The quantitative imaging and analysis methods are based on the dynamic analysis approach, which generates a fast matrix transform for projection of list-mode PIXE data onto pure elemental images. Recent advances provide rapid pixel-by-pixel correction for matrix and absorption effects in different (mineral) compositions across the image area to yield true quantitative images. These methods are combined in a software package called GeoPIXE II10 page(s

Cortical synaptic and dendritic spine abnormalities in a presymptomatic TDP-43 model of amyotrophic lateral sclerosis

Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of motor output. In amyotrophic lateral sclerosis (ALS) LVPNs and spinal motor neurons degenerate. The pathogenesis of neural degeneration is unknown in ALS; 10% of cases have a genetic cause, whereas 90% are sporadic, with most of the latter showing TDP-43 inclusions. Clinical and experimental evidence implicate excitotoxicity as a prime aetiological candidate. Using patch clamp and dye-filling techniques in brain slices, combined with high-resolution confocal microscopy, we report increased excitatory synaptic inputs and dendritic spine densities in early presymptomatic mice carrying a TDP-43 Q331K mutation. These findings demonstrate substantive alterations in the motor cortex neural network, long before an overt degenerative phenotype has been reported. We conclude that increased excitatory neurotransmission is a common pathophysiology amongst differing genetic cases of ALS and may be of relevance to the 95% of sporadic ALS cases that exhibit TDP-43 inclusions