Fast-spiking interneurones (FSIs) constitute a prominent part of the inhibitory microcircuitry of... more Fast-spiking interneurones (FSIs) constitute a prominent part of the inhibitory microcircuitry of the striatum; however, little is known about their recruitment by synaptic inputs in vivo. Here, we report that, in contrast to cholinergic interneurones (CINs), FSIs (n = 9) recorded in urethane-anaesthetized rats exhibit Down-to-Up state transitions very similar to spiny projection neurones (SPNs). Compared to SPNs, the FSI Up state membrane potential was noisier and power spectra exhibited significantly larger power at frequencies in the gamma range (55-95 Hz). The membrane potential exhibited short and steep trajectories preceding spontaneous spike discharge, suggesting that fast input components controlled spike output in FSIs. Spontaneous spike data contained a high proportion (43.6 ± 32.8%) of small inter-spike intervals (ISIs) of <30 ms, setting FSIs clearly apart from SPNs and CINs. Cortical-evoked inputs had slower dynamics in SPNs than FSIs, and repetitive stimulation entr...
Following a cerebral cortex injury such as stroke, excessive inhibition around the core of the in... more Following a cerebral cortex injury such as stroke, excessive inhibition around the core of the injury is thought to reduce the potential for new motor learning. In part, this may be caused by an imbalance of interhemispheric inhibition (IHI); therefore, treatments that relieve the inhibitory drive from the healthy hemisphere to the peri-lesional area may enhance motor recovery. Theta burst stimulation delivered by transcranial magnetic stimulation has been tested as a means of normalizing IHI, but clinical results have been variable. Here we use a new rat model of synaptic IHI to demonstrate that electrical intracranial theta burst stimulation causes long-lasting changes in motor cortex excitability. Further, we show that contralateral intermittent theta burst stimulation (iTBS) blocks IHI via a mechanism involving cannabinoid receptors. Finally, we show that contralesional iTBS applied during recovery from cortical injury in rats improves the recovery of motor function. These findi...
To investigate the prevalence of hepatitis C antibody (anti-HCV) in injecting drug users (IDU), p... more To investigate the prevalence of hepatitis C antibody (anti-HCV) in injecting drug users (IDU), particularly amongst those of recent onset beginning since the advent of the needle-exchange programme. Secondly this study sought information on needle-sharing practices. The records of injecting drug users over 2 years from January 1992 were examined for anti-HCV results and needle-sharing reports on initial assessment at the Wellington drug dependency clinic. Amongst 110 injecting drug users 92 (84%) were tested for anti-HCV, and 71 (77%) were positive. There was a significant (p = 0.02) association between the reported duration of intravenous drug misuse and the proportion of injecting drug users who were positive for anti-HCV. Of those injecting drug users who had reported use of less than 4 years, since the introduction of the New Zealand needle exchange programme, 53% were positive for anti-HCV. Needle-sharing was frequently reported to have ever occurred in 74% of these patients at some time, and in 64% of those who reported use of less than 4 years. These differences were not significant. However, in the period before presenting 67% had not shared over the last 3 months and 57% had not shared over the previous 1 year, which are improvements on previous studies of needle-sharing, considered to be the most important mode of transmission for blood-borne viruses in injecting drug users. These results suggest considerable potential for HIV infection rates among injecting drug users in New Zealand to increase from the current low level. There needs to be continuing emphasis on public health programmes to eradicate needle-sharing, and to promote safe injecting techniques for injecting drug users.
This paper describes the circuitry and construction of a novel electronic threshold discriminator... more This paper describes the circuitry and construction of a novel electronic threshold discriminator, and details its specific application to in vivo intracellular recording. The discriminator reliably triggers electrophysiological recording at pre-selectable membrane potentials in neuronal systems that exhibit membrane potential oscillations. It has been used successfully whilst recording from spiny projection neurons of the striatum to measure membrane properties and trigger electrical stimulation within either of two discrete membrane potential &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;states&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. The device works by comparing the analogue membrane potential waveform with a user-defined threshold membrane potential, and outputs a logic signal to flag the occurrence of a threshold-crossing event. This signal is used to trigger the commencement of episodic recording and the application of current injection or electrical stimulation at a consistent membrane potential. Thus, the discriminator acts as a functional clamp to isolate evoked responses from endogenous fluctuations in membrane potential. The unit uses cheap and easily available components and can be constructed with the minimum of electronics experience. It could be adapted to isolate discrete events within any oscillatory system.
Tonically active neurons (TANs) in the mammalian striatum show a pause in their ongoing firing ac... more Tonically active neurons (TANs) in the mammalian striatum show a pause in their ongoing firing activity in response to an auditory cue that is paired with a reward. This response to reward-related cues develops through learning and becomes expressed synchronously by TANs located throughout the striatum. The pause response is abolished by inactivating the thalamic inputs to the striatum but a short-latency excitatory response to reward-related cues remains, which may originate in the cortex. We investigated the cortical inputs to striatal neurons to determine the electrophysiological properties of their cortical projections. We made in vivo intracellular recordings from 14 giant aspiny interneurons (which correspond to the TANs) and from a control group of spiny projection neurons (n=18) in urethane-anaesthetised rats. All giant aspiny interneurons were tonically active (firing rate: 3.0+/-1.5 Hz) and displayed small-amplitude subthreshold fluctuations in membrane potential. These fluctuations in membrane potential were correlated with the cortical electroencephalogram (EEG). Test stimulation of the contralateral cortex induced postsynaptic potentials (PSPs) in giant aspiny interneurons. These PSPs were significantly shorter in latency (5.1+/-1.6 ms) than those measured in spiny projection neurons (9.3+/-2.8 ms; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), whereas the latencies of ipsilaterally evoked PSPs did not differ. Taken together, these observations suggest that giant aspiny interneurons are under the significant influence of spontaneous excitatory inputs and receive specialised input from either faster conducting or less branching cortical fibres than spiny projection neurons. These inputs may be involved in the synchronised convergence of reward-related cues from spatially distinct cortical areas onto giant aspiny interneurons.
Fast-spiking interneurones (FSIs) constitute a prominent part of the inhibitory microcircuitry of... more Fast-spiking interneurones (FSIs) constitute a prominent part of the inhibitory microcircuitry of the striatum; however, little is known about their recruitment by synaptic inputs in vivo. Here, we report that, in contrast to cholinergic interneurones (CINs), FSIs (n = 9) recorded in urethane-anaesthetized rats exhibit Down-to-Up state transitions very similar to spiny projection neurones (SPNs). Compared to SPNs, the FSI Up state membrane potential was noisier and power spectra exhibited significantly larger power at frequencies in the gamma range (55-95 Hz). The membrane potential exhibited short and steep trajectories preceding spontaneous spike discharge, suggesting that fast input components controlled spike output in FSIs. Spontaneous spike data contained a high proportion (43.6 ± 32.8%) of small inter-spike intervals (ISIs) of <30 ms, setting FSIs clearly apart from SPNs and CINs. Cortical-evoked inputs had slower dynamics in SPNs than FSIs, and repetitive stimulation entr...
Following a cerebral cortex injury such as stroke, excessive inhibition around the core of the in... more Following a cerebral cortex injury such as stroke, excessive inhibition around the core of the injury is thought to reduce the potential for new motor learning. In part, this may be caused by an imbalance of interhemispheric inhibition (IHI); therefore, treatments that relieve the inhibitory drive from the healthy hemisphere to the peri-lesional area may enhance motor recovery. Theta burst stimulation delivered by transcranial magnetic stimulation has been tested as a means of normalizing IHI, but clinical results have been variable. Here we use a new rat model of synaptic IHI to demonstrate that electrical intracranial theta burst stimulation causes long-lasting changes in motor cortex excitability. Further, we show that contralateral intermittent theta burst stimulation (iTBS) blocks IHI via a mechanism involving cannabinoid receptors. Finally, we show that contralesional iTBS applied during recovery from cortical injury in rats improves the recovery of motor function. These findi...
To investigate the prevalence of hepatitis C antibody (anti-HCV) in injecting drug users (IDU), p... more To investigate the prevalence of hepatitis C antibody (anti-HCV) in injecting drug users (IDU), particularly amongst those of recent onset beginning since the advent of the needle-exchange programme. Secondly this study sought information on needle-sharing practices. The records of injecting drug users over 2 years from January 1992 were examined for anti-HCV results and needle-sharing reports on initial assessment at the Wellington drug dependency clinic. Amongst 110 injecting drug users 92 (84%) were tested for anti-HCV, and 71 (77%) were positive. There was a significant (p = 0.02) association between the reported duration of intravenous drug misuse and the proportion of injecting drug users who were positive for anti-HCV. Of those injecting drug users who had reported use of less than 4 years, since the introduction of the New Zealand needle exchange programme, 53% were positive for anti-HCV. Needle-sharing was frequently reported to have ever occurred in 74% of these patients at some time, and in 64% of those who reported use of less than 4 years. These differences were not significant. However, in the period before presenting 67% had not shared over the last 3 months and 57% had not shared over the previous 1 year, which are improvements on previous studies of needle-sharing, considered to be the most important mode of transmission for blood-borne viruses in injecting drug users. These results suggest considerable potential for HIV infection rates among injecting drug users in New Zealand to increase from the current low level. There needs to be continuing emphasis on public health programmes to eradicate needle-sharing, and to promote safe injecting techniques for injecting drug users.
This paper describes the circuitry and construction of a novel electronic threshold discriminator... more This paper describes the circuitry and construction of a novel electronic threshold discriminator, and details its specific application to in vivo intracellular recording. The discriminator reliably triggers electrophysiological recording at pre-selectable membrane potentials in neuronal systems that exhibit membrane potential oscillations. It has been used successfully whilst recording from spiny projection neurons of the striatum to measure membrane properties and trigger electrical stimulation within either of two discrete membrane potential &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;states&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. The device works by comparing the analogue membrane potential waveform with a user-defined threshold membrane potential, and outputs a logic signal to flag the occurrence of a threshold-crossing event. This signal is used to trigger the commencement of episodic recording and the application of current injection or electrical stimulation at a consistent membrane potential. Thus, the discriminator acts as a functional clamp to isolate evoked responses from endogenous fluctuations in membrane potential. The unit uses cheap and easily available components and can be constructed with the minimum of electronics experience. It could be adapted to isolate discrete events within any oscillatory system.
Tonically active neurons (TANs) in the mammalian striatum show a pause in their ongoing firing ac... more Tonically active neurons (TANs) in the mammalian striatum show a pause in their ongoing firing activity in response to an auditory cue that is paired with a reward. This response to reward-related cues develops through learning and becomes expressed synchronously by TANs located throughout the striatum. The pause response is abolished by inactivating the thalamic inputs to the striatum but a short-latency excitatory response to reward-related cues remains, which may originate in the cortex. We investigated the cortical inputs to striatal neurons to determine the electrophysiological properties of their cortical projections. We made in vivo intracellular recordings from 14 giant aspiny interneurons (which correspond to the TANs) and from a control group of spiny projection neurons (n=18) in urethane-anaesthetised rats. All giant aspiny interneurons were tonically active (firing rate: 3.0+/-1.5 Hz) and displayed small-amplitude subthreshold fluctuations in membrane potential. These fluctuations in membrane potential were correlated with the cortical electroencephalogram (EEG). Test stimulation of the contralateral cortex induced postsynaptic potentials (PSPs) in giant aspiny interneurons. These PSPs were significantly shorter in latency (5.1+/-1.6 ms) than those measured in spiny projection neurons (9.3+/-2.8 ms; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), whereas the latencies of ipsilaterally evoked PSPs did not differ. Taken together, these observations suggest that giant aspiny interneurons are under the significant influence of spontaneous excitatory inputs and receive specialised input from either faster conducting or less branching cortical fibres than spiny projection neurons. These inputs may be involved in the synchronised convergence of reward-related cues from spatially distinct cortical areas onto giant aspiny interneurons.
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