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In the monkey, reaction time in a precued delayed response task was found to be faster when the animals had to remember the precue than when it was continually available (Smyrnis, Taira, Ashe, & Georgopoulos, 1992). We investigated whether this reflects a general principle that applies to all types of precued tasks. However, we found the opposite result in a simpler task in humans. Our findings suggest that the beneficial effect of a memory requirement on reaction time in the monkey may reflect an effect of task difficulty, rather than a fundamental process involved in all precued movement tasks. [ABSTRACT FROM AUTHOR]

The effect of foreperiod length on reaction time in memorized (MM) and nonmemorized (NM), precued, delayed responses was investigated. Six subjects participated in one long and one short foreperiod schedule testing session. An aiming task, using elbow supination/pronation, in response to a visual stimulus was employed. In the MM condition, target spatial information was available for a fraction of the foreperiod duration. In the NM condition, target information was available continuously until the subject attained the target position. Subjects responded with a significantly longer latency in the long foreperiod schedule. Within each foreperiod schedule, the shortest foreperiod resulted in significantly longer reaction time. However, the absolute value of foreperiod did not have a major effect on reaction time latency. Memorization and nonmemorization conditions did not affect reaction time. [ABSTRACT FROM AUTHOR]

Examines the equipotent dose comparison of haloperidol and raclopride dopamines during a learned motor task in New Zealand. Clinical use of haloperidol; Utilization of the physiological saline injections as a control; Details on the control levels of both dopamines.

Presents an abstract of the study 'Foreperiod Length, but not Memory, Affects Human Reaction Time in a Pre-cued, Delayed Response Task,' submitted to the Fifteenth International Australasian Winter Conference on Brain Research in Queenstown, New Zealand in August to September 1997.

Parkinson's disease (PD) is a motor disorder charactertised by altered neural activity throughout the basal ganglia-thalamocortical circuit. Electrical deep brain stimulation (DBS) is efficacious in alleviating motor symptoms, but has several notable side-effects, most likely reflecting the non-specific nature of electrical stimulation and/or the brain regions targeted. We determined whether specific optogenetic activation of glutamatergic motor thalamus (Mthal) neurons alleviated forelimb akinesia in a chronic rat model of PD. Parkinsonian rats (unilateral 6-hydroxydopamine injection) were injected with an adeno-associated viral vector (AAV5-CaMKII-Chrimson-GFP) to transduce glutamatergic Mthal neurons with the red-shifted Chrimson opsin. Optogenetic stimulation with orange light at 15 Hz tonic and a physiological pattern, previously recorded from a Mthal neuron in a control rat, significantly increased forelimb use in the reaching test (p < 0.01). Orange light theta burst stimulation, 15 Hz and control reaching patterns significantly reduced akinesia (p < 0.0001) assessed by the step test. In contrast, forelimb use in the cylinder test was unaffected by orange light stimulation with any pattern. Blue light (control) stimulation failed to alter behaviours. Activation of Chrimson using complex patterns in the Mthal may be an alternative treatment to recover movement in PD. These vector and opsin changes are important steps towards translating optogenetic stimulation to humans., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Action stopping depends on at least two (fast, slow) frontal circuits depending on the urgency of execution of the 'go' response. Human EEG suggests a third (even slower, limbic) circuit that activates frontal areas at frequencies typical of 'hippocampal theta'. Here we test in male rats whether stop-go conflict engages the hippocampus and so may send theta-modulated information via the frontal cortex to the subthalamic nucleus. We recorded from multi-electrode arrays in the hippocampus, orbitofrontal cortex, and subthalamus in 5 male Long Evans rats performing a stop signal task and, as in previous human experiments, assessed stop-signal specific power for effects of goal conflict. Conflict increased 11-12 Hz theta power modestly in all three structures but with the largest increase in power being at 5 Hz in the frontal cortex but not the hippocampus. There was increased conflict-related coherence in all circuits in the range 5-8 Hz and particularly at 5-6 Hz. Increased coherence coupled with an increase in conflict-induced low frequency power in the frontal cortex may reflect communication with the hippocampus. The data are consistent with a third limbic circuit that can generate stopping when go responses are particularly slow (as, e.g., in a go/no go task). [199 words; 200 max]., (Copyright © 2022 Japan Neuroscience Society and Elsevier B.V. All rights reserved.)

A hippocampal-diencephalic-cortical network supports memory function. The anterior thalamic nuclei (ATN) form a key anatomical hub within this system. Consistent with this, injury to the mammillary body-ATN axis is associated with examples of clinical amnesia. However, there is only limited and indirect support that the output of ATN neurons actively enhances memory. Here, in rats, we first showed that mammillothalamic tract (MTT) lesions caused a persistent impairment in spatial working memory. MTT lesions also reduced rhythmic electrical activity across the memory system. Next, we introduced 8.5 Hz optogenetic theta-burst stimulation of the ATN glutamatergic neurons. The exogenously-triggered, regular pattern of stimulation produced an acute and substantial improvement of spatial working memory in rats with MTT lesions and enhanced rhythmic electrical activity. Neither behaviour nor rhythmic activity was affected by endogenous stimulation derived from the dorsal hippocampus. Analysis of immediate early gene activity, after the rats foraged for food in an open field, showed that exogenously-triggered ATN stimulation also increased Zif268 expression across memory-related structures. These findings provide clear evidence that increased ATN neuronal activity supports memory. They suggest that ATN-focused gene therapy may be feasible to counter clinical amnesia associated with dysfunction in the mammillary body-ATN axis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V.)

L-DOPA is the primary pharmacological treatment for relief of the motor symptoms of Parkinson's disease (PD). With prolonged treatment (⩾5 years) the majority of patients will develop abnormal involuntary movements as a result of L-DOPA treatment, known as L-DOPA-induced dyskinesia. Understanding the underlying mechanisms of dyskinesia is a crucial step toward developing treatments for this debilitating side effect. We used the 6-hydroxydopamine (6-OHDA) rat model of PD treated with a three-week dosing regimen of L-DOPA plus the dopa decarboxylase inhibitor benserazide (4 mg/kg and 7.5 mg/kgs.c., respectively) to induce dyskinesia in 50% of individuals. We then used RNA-seq to investigate the differences in mRNA expression in the striatum of dyskinetic animals, non-dyskinetic animals, and untreated parkinsonian controls at the peak of dyskinesia expression, 60 min after L-DOPA administration. Overall, 255 genes were differentially expressed; with significant differences in mRNA expression observed between all three groups. In dyskinetic animals 129 genes were more highly expressed and 14 less highly expressed when compared with non-dyskinetic and untreated parkinsonian controls. In L-DOPA treated animals 42 genes were more highly expressed and 95 less highly expressed when compared with untreated parkinsonian controls. Gene set cluster analysis revealed an increase in expression of genes associated with the cytoskeleton and phosphoproteins in dyskinetic animals compared with non-dyskinetic animals, which is consistent with recent studies documenting an increase in synapses in dyskinetic animals. These genes may be potential targets for drugs to ameliorate L-DOPA-induced dyskinesia or as an adjunct treatment to prevent their occurrence., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

The goal of the present study was to determine the phase relationships of the slow oscillatory activity that emerges in basal ganglia nuclei in anesthetized rats after dopamine cell lesion in order to gain insight into the passage of this oscillatory activity through the basal ganglia network. Spike train recordings from striatum, subthalamic nucleus (STN), globus pallidus (GP), and substantia nigra pars reticulata (SNpr) were paired with simultaneous local field potential (LFP) recordings from SNpr or motor cortex ipsilateral to a unilateral lesion of substantia nigra dopamine neurons in urethane-anesthetized rats. Dopamine cell lesion induced a striking increase in incidence of slow oscillations (0.3-2.5 Hz) in firing rate in all nuclei. Phase relationships assessed through paired recordings using SNpr LFP as a temporal reference showed that slow oscillatory activity in GP spike trains is predominantly antiphase with oscillations in striatum, and slow oscillatory activity in STN spike trains is in-phase with oscillatory activity in cortex but predominantly antiphase with GP oscillatory activity. Taken together, these results imply that after dopamine cell lesion in urethane-anesthetized rats, increased oscillatory activity in GP spike trains is shaped more by increased phasic inhibitory input from the striatum than by phasic excitatory input from STN. In addition, results show that oscillatory activity in SNpr spike trains is typically antiphase with GP oscillatory activity and in-phase with STN oscillatory activity. While these observations do not rule out additional mechanisms contributing to the emergence of slow oscillations in the basal ganglia after dopamine cell lesion in the anesthetized preparation, they are compatible with 1) increased oscillatory activity in the GP facilitated by an effect of dopamine loss on striatal 'filtering' of slow components of oscillatory cortical input, 2) increased oscillatory activity in STN spike trains supported by convergent antiphase inhibitory and excitatory oscillatory input from GP and cortex, respectively, and 3) increased oscillatory activity in SNpr spike trains organized by convergent antiphase inhibitory and excitatory oscillatory input from GP and STN, respectively.