Biomedical subjects

John N J Reynolds

Publications and source records attributed to John N J Reynolds.

5 recordsLinked to original sources

PubMed2004

Modulation of an afterhyperpolarization by the substantia nigra induces pauses in the tonic firing of striatal cholinergic interneurons.

Striatal cholinergic interneurons, also known as tonically active neurons (TANs), acquire a pause in firing during learning of stimulus-reward associations. This pause response to a sensory stimulus emerges after repeated pairing with a reward. The conditioned pause is dependent on dopamine from the substantia nigra, but its underlying cellular mechanism is unknown. Using in vivo intracellular recording, we found that both subthreshold and suprathreshold depolarizations in cholinergic interneurons induced a prolonged after-hyperpolarization (AHP) associated with a pause in their tonic firing. The AHP duration was dependent on the level of depolarization, whether elicited by intracellular current injection or by activation of excitatory inputs from the cortex. High-frequency stimulation of the substantia nigra induced potentiation of the cortically evoked excitation and increased the prolonged AHP after the stimulus. These findings from anesthetized animals suggest that a substantia nigra-induced AHP produces stimulus-associated firing pauses in cholinergic interneurons. This mechanism may underlie the acquisition of the pause response in TANs recorded from behaving animals during learning.

Action Potentials↗

PubMed2004

The corticostriatal input to giant aspiny interneurons in the rat: a candidate pathway for synchronising the response to reward-related cues.

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<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.

Action Potentials↗

PubMed2003

A state-dependent trigger for electrophysiological recording at predetermined membrane potentials.

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 "states". 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.

Amplifiers, Electronic↗

PubMed2003

Neural mechanisms of reward-related motor learning.

The analysis of the neural mechanisms responsible for reward-related learning has benefited from recent studies of the effects of dopamine on synaptic plasticity. Dopamine-dependent synaptic plasticity may lead to strengthening of selected inputs on the basis of an activity-dependent conjunction of sensory afferent activity, motor output activity, and temporally related firing of dopamine cells. Such plasticity may provide a link between the reward-related firing of dopamine cells and the acquisition of changes in striatal cell activity during learning. This learning mechanism may play a special role in the translation of reward signals into context-dependent response probability or directional bias in movement responses.

Animals↗

PubMedDate not supplied

Dopamine-dependent plasticity of corticostriatal synapses.

Knowledge of the effect of dopamine on corticostriatal synaptic plasticity has advanced rapidly over the last 5 years. We consider this new knowledge in relation to three factors proposed earlier to describe the rules for synaptic plasticity in the corticostriatal pathway. These factors are a phasic increase in dopamine release, presynaptic activity and postsynaptic depolarisation. A function is proposed which relates the amount of dopamine release in the striatum to the modulation of corticostriatal synaptic efficacy. It is argued that this function, and the experimental data from which it arises, are compatible with existing models which associate the reward-related firing of dopamine neurons with changes in corticostriatal synaptic efficacy.

Afferent Pathways↗