High‐frequency deep brain stimulation (HFS‐DBS) of the subcallosal cingulate (SCC) region has been investigated as a treatment for refractory forms of depression with a ~50% remission rate in open ...label studies. However, the therapeutic mechanisms of DBS are still largely unknown. Using anaesthetized Sprague Dawley rats, we recorded neuronal spiking activity in 102 neurons of the dorsal raphe (DR) before, during and after the induction of a 5‐min HFS train in the infralimbic region (IL) of the medial prefrontal cortex (mPFC), the rodent homologue of the human SCC. The majority of DR cells (82%) significantly decreased firing rate during HFS (P < 0.01, 55.7 ± 4.5% of baseline, 35 rats). To assess whether mPFC‐HFS mediates inhibition of DR cellular firing by stimulating local GABAergic interneurons, the GABAA antagonist bicuculline (Bic, 100 μm) was injected directly into the DR during HFS. Neurons inhibited by HFS recovered their firing rate during Bic+HFS (P < 0.01, n = 15, seven rats) to levels not different from baseline. Cells that were not affected by HFS did not change firing rate during Bic+HFS (P = 0.968, n = 7, three rats). These results indicate that blocking GABAA reverses HFS‐mediated inhibition of DR neurons. As the cells that were not inhibited by HFS were also unaffected by HFS+Bic, they are probably not innervated by local GABA. Taken together, our results suggest that mPFC‐HFS may exert a preferential effect on DR neurons with GABAA receptors.
The medial prefrontal cortex (mPFC) exerts descending control over cortical projecting neurons in the dorsal raphe (DR), which suggests an important role for DR afferent systems in emotional modulation. Results presented here show that high frequency stimulation (HFS) of the infralimbic region (IL) of the mPFC decreases cellular firing in the DR. Locally injecting GABAA receptor antagonist bicuculline into the DR during HFS recovered cellular firing to baseline levels. These results indicate that mPFC‐HFS exerts a preferential effect on DR neurons with GABAA receptors.
Modern functional neurosurgery for movement disorders such as Parkinson's disease, tremor, and dystonia involves the placement of focal lesions or the application of deep brain stimulation (DBS) ...within circuits that modulate motor function. Precise targeting of these motor structures can be further refined by the use of electrophysiological approaches. In particular, microelectrode recordings enable the delineation of neuroanatomic structures. In the course of these operations, there is an opportunity not only to map basal ganglia structures but also to gain insights into how disturbances in neural activity produce movement disorders. In this review, we aim to highlight what the field has uncovered thus far about movement disorders through DBS. The work to date lays the foundation for future studies that will shed further light on dysfunctional circuits mediating diseases of the nervous system and how we might modulate these circuits therapeutically.
Abstract
Minnesota was dubbed the ‘raspberry consumption capital of America’ in 2017 by wholesaler Driscoll’s, Inc. Local production of this high-demand fruit, however, is limited by the invasive ...pest, spotted wing Drosophila (Drosophila suzukii Matsumura, Diptera: Drosophilidae). Recent research to develop integrated pest management (IPM) programs for MN berry crops indicates that raspberry growers are particularly vulnerable to significant spotted wing Drosophila-related yield losses. Spotted wing Drosophila was detected in Minnesota in 2012 across 29 counties. This analysis explores the economic impact of raspberry yield losses associated with spotted wing Drosophila in Minnesota as part of a multifaceted research initiative. An electronic survey of 157 MN berry growers was conducted in November 2017. Eighty-two individual grower surveys were returned (52% response rate). The survey included questions about production acreage, marketing practices, spotted wing Drosophila-related yield losses and future production intentions. The results of the e-survey indicate that raspberry growers have borne the highest levels of infestation among MN fruit growers surveyed. Spotted wing Drosophila-related yield losses for raspberry growers ranged from 2 to 100% of planted acreage.The median yield loss for this group of growers was 20% in 2017. Applying the median yield loss to ex-ante production estimates, we conclude that MN growers lost approximately $2.36 million in raspberry sales during the 1 yr studied. Investing in spotted wing Drosophila control measures will help MN growers reduce some of these losses in the future.
Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its ...mechanism of action have not been fully characterized.
The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr).
Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for Parkinson's disease (PD). Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode.
Inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .013). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation but not in SNr (p < .001) where depression of inhibitory input was coupled with a return of neuronal firing (p = .003).
Persistent inhibitory input to the STN suggests a local synaptic mechanism for the suppression of subthalamic firing during high frequency stimulation. Moreover, differences in the resiliency versus vulnerability of inhibitory inputs to the STN and SNr suggest a projection source- and frequency-specificity for this mechanism. The feasibility of targeting electrophysiologically-identified neural structures may provide insight into how DBS achieves frequency-specific modulation of neuronal projections.
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•In the STN, extracellular stimulation elicits excitatory and inhibitory effects•STN evoked field responses are predictive of bidirectional effects on firing rates•Persistent synaptic inhibition at high stimulation frequencies in STN, but not SNr•Synaptic inhibition at DBS targets is frequency- and projection-source specific•Synaptic dynamics may justify DBS frequency selection
Highlights ► 30% of globus pallidus neurons in Parkinson’s disease patients have 11–30 Hz beta oscillatory activity. ► Globus pallidus firing is coherent with the local field potential (LFP) ...oscillatory activity in the beta range. ► In dystonia patients LFP and neuronal oscillatory activity frequency is 8–10 Hz and only 10% of neurons fire coherently.
There is growing evidence that Parkinson's disease (PD) is associated with pathological synchronous oscillatory activity in the basal ganglia. These synchronized oscillations primarily occur in the ...11–30 Hz range, the so-called beta band. Studies of local field potential activity in the subthalamic nucleus (STN) of PD patients suggest that exaggerated beta band oscillatory activity can disrupt function and, in particular, may contribute to slowness of movement. It has been previously shown that the degree of beta oscillatory activity in the STN of PD patients correlates with the patients' benefit from dopaminergic medications, but not with baseline motor deficits. In a paper that was recently published in
Experimental Neurology, Kuhn A.A., Tsui A., Aziz T., Ray N., Brucke C., Kupsch A., Schneider G.H., Brown P., 2009. Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity. Exp. Neurol. 215, 380–387. the authors further establish that the degree of suppression of beta oscillations in the STN by dopaminergic medications can predict the level of improvement in bradykinesia and rigidity but not tremor. This commentary reviews some of the recent findings on beta oscillatory activity in PD and highlights the possible role of these pathological oscillations in mediating PD symptoms.
Chilo partellus
is a major crop pest in Asia and Africa, and has recently spread to the Mediterranean region. Knowledge of its potential distribution can inform biosecurity policies aimed at limiting ...its further spread and efforts to reduce its impact in areas that are already invaded. Three models of the potential distribution of this insect have been published, each with significant shortcomings. We re-parameterized an existing CLIMEX model to address some parameter inconsistencies and to improve the fit to the known distribution of
C. partellus
. The resulting model fits the known distribution better than previous models, highlights additional risks in equatorial regions and reduces modelled risks in wet and extremely dry regions. We bring new insights into the role of irrigation in the potential spread of this invasive insect and compare its potential distribution with the present known distribution of its hosts. We also distinguish regions that are suitable for supporting persistent populations from those that may be at risk from ephemeral populations during favourable seasons. We present one of the first demonstrations of a new capability in CLIMEX to automatically estimate parameter sensitivity and model uncertainty. Our CLIMEX model highlights the substantial invasion risk posed by
C. partellus
to cropping regions in the Americas, Australia, China, Europe, New Zealand and West Africa. Its broad host range and reported impacts suggest that it should be a pest of significant concern to biosecurity agencies in these presently uninvaded regions.
Abstract The subcallosal cingulate (SCC) region, or its rodent homologue the medial prefrontal cortex (mPFC), and midbrain dorsal raphe (DR) are crucial nodes of the widespread network implicated in ...emotional regulation. Stimulation of the SCC is being explored as a potential treatment for depression. Because modulation of the 5-HT system is the most common pharmacological means of treating depression, we sought to establish 5-HT's role in the mPF C -DR projection. Using anaesthetized mice, we recorded neuronal activity in 49 neurons of the DR before, during, and after high frequency stimulation (HFS) of the mPFC. The majority of DR cells (74%) significantly decreased firing rate during HFS ( p < 0.001, 65.7 ± 9.4% of baseline, 14 mice). To see the effect of mPFC-HFS on 5-HT neurons, we used transgenic mice with expression of the channelrhodopsin fusion protein directed to the 5-HT neuron population. Neurons were categorized as 5-HT based on their excitatory response to blue light stimulation ( p < 0.05, n = 11). Our main finding was that identified 5-HT neurons in the DR were clearly inhibited by HFS, albeit non-selectively. Lastly, we used fast scan cyclic voltammetry (FSCV) to investigate the effects of mPFC-HFS on the release and reuptake of electrically stimulated 5-HT in the DR of C57BL/6 J mice. Serotonin clearance was significantly faster following 5 min HFS (2.3 ± 1.0 s, n = 5, p < 0.05) when compared to control levels (3.7 ± 1.0 s, n = 5), indicating less release or more efficient 5-HT reuptake. Taken together, these findings imply that mPFC stimulation alters 5-HT activity dynamics in the DR. Such altered 5-HT dynamics may modulate the potential therapeutic mechanisms of SCC/mPFC stimulation.
Deep brain stimulation (DBS) in the globus pallidus internus (GPi) has been shown to improve dystonia, a movement disorder of repetitive twisting movements and postures. DBS at frequencies above 60 ...Hz improves dystonia, but the mechanisms underlying this frequency dependence are unclear. In patients undergoing dual-microelectrode mapping of the GPi, microstimulation has been shown to reduce neuronal firing, presumably due to synaptic GABA release. This study examined the effects of different microstimulation frequencies (1-100 Hz) and train length (0.5-20 s), with and without prior high-frequency stimulation (HFS) on neuronal firing and evoked field potentials (fEPs) in 13 dystonia patients. Pre-HFS, the average firing decreased as stimulation frequency increased and was silenced above 50 Hz. The average fEP amplitudes increased up to frequencies of 20-30 Hz but then declined and at 50 Hz, were only at 75% of baseline. In some cases, short latency fiber volleys and antidromic-like spikes were observed and followed high frequencies. Post-HFS, overall firing was reduced compared with pre-HFS, and the fEP amplitudes were enhanced at low frequencies, providing evidence of inhibitory synaptic plasticity in the GPi. In a patient with DBS electrodes already implanted in the GPi, recordings from four neurons in the subthalamic nucleus showed almost complete inhibition of firing with clinically effective but not clinically ineffective stimulation parameters. These data provide additional support for the hypothesis of stimulation-evoked GABA release from afferent synaptic terminals and reduction of neuronal firing during DBS and additionally, implicate excitation of GPi axon fibers and neurons and enhancement of inhibitory synaptic transmission by high-frequency GPi DBS as additional putative mechanisms underlying the clinical benefits of DBS in dystonia.
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