Wireless powering of magnetoelectric nanoelectrodes is used for deep brain stimulation in freely moving and transgene-free mice.

Deep brain stimulation (DBS) is among the most successful paradigms in both translational and reverse translational neuroscience. DBS has developed into a standard treatment for movement disorders such as Parkinson’s disease (PD) in recent decades, however, specific mechanisms behind DBS’s efficacy and side effects remain unrevealed. Several hypotheses have been proposed, including neuronal firing rate and pattern theories that emphasize the impact of DBS on local circuitry but detail distant electrophysiological readouts to a lesser extent. Furthermore, ample preclinical and clinical evidence indicates that DBS influences neurotransmitter dynamics in PD, particularly the effects of subthalamic nucleus (STN) DBS on striatal dopaminergic and glutamatergic systems; pallidum DBS on striatal dopaminergic and GABAergic systems; pedunculopontine nucleus DBS on cholinergic systems; and STN-DBS on locus coeruleus (LC) noradrenergic system. DBS has additionally been associated with mood-related side effects within brainstem serotoninergic systems in response to STN-DBS. Still, addressing the mechanisms of DBS on neurotransmitters’ dynamics is commonly overlooked due to its practical difficulties in monitoring real-time changes in remote areas. Given that electrical stimulation alters neurotransmitter release in local and remote regions, it eventually exhibits changes in specific neuronal functions. Consequently, such changes lead to further modulation, synthesis, and release of neurotransmitters. This narrative review discusses the main neurotransmitter dynamics in PD and their role in mediating DBS effects from preclinical and clinical data.

Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has gained interest as a potential therapy for treatment-resistant dementia. However, optimal stimulation parameters and mechanisms of action are yet to be elucidated. First, we assessed NBM DBS at different stimulation parameters in a scopolamine-induced rat model of dementia. Rats were tested in the object location task with the following conditions: (i) low and high frequency (20 Hz or 120 Hz), (ii) monophasic or biphasic pulse shape (iii) continuous or intermittent DBS (20s on, 40s off) and 100 μA amplitude. Thereafter, rats were stimulated with the most effective parameter followed by 5-bromo-2'-deoxyuridine (BrdU) administration and perfused 4 weeks later. We then evaluated the effects of NBM DBS on hippocampal neurogenesis, synaptic plasticity, and on cholinergic fibres in the perirhinal and cingulate cortex using immunohistochemistry. We also performed in-vivo microdialysis to assess circuit-wide effects of NBM DBS on hippocampal acetylcholine levels during on and off stimulation. Biphasic, low frequency and intermittent NBM DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that acute stimulation promoted proliferation in the dentate gyrus, increased synaptic plasticity in the CA1 and CA3 subregion of the hippocampus, and increased length of cholinergic fibres in the cingulate gyrus. There was no difference regarding hippocampal acetylcholine levels between the groups. These findings suggest that the potential mechanism of action of the induced memory enhancement through NBM DBS might be due to selective neuroplastic and neurochemical changes.

Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and stimulation regimens remain to be defined. Herein, we investigated metabolic and neuronal activity changes using cytochrome C oxidase histochemistry and c-Fos immunohistochemistry in a noise trauma-induced rat model of tinnitus. We also assessed changes in neuronal activity following medial geniculate body (MGB) high-frequency stimulation (HFS). Metabolic activity was reduced in the primary auditory cortex, MGB and CA1 region of the hippocampus in noise-exposed rats. Additionally, c-Fos expression was increased in the primary auditory cortex of those animals. Furthermore, MGB-HFS enhanced c-Fos expression in the thalamic reticular nucleus. We concluded that noise trauma alters tissue activity in multiple brain areas including the auditory and limbic regions. MGB-HFS resulted in higher neuronal activity in the thalamic reticular nucleus. Given the prominent role of the auditory thalamus in tinnitus, these data provide more rationales towards targeting the MGB with HFS as a symptom management tool in tinnitus.

A wide range of neuromodulation technologies has been explored for their applicability and effectiveness in modulating neural tissue, ranging from tethered devices to nano-scale approaches [1-3]. N...

Tinnitus is the phantom perception of a sound, often accompanied by increased anxiety and depressive symptoms. Degenerative or inflammatory processes, as well as changes in monoaminergic systems, have been suggested as potential underlying mechanisms. Herein, we conducted the first post-mortem histopathological assessment to reveal detailed structural changes in tinnitus patients’ auditory and non-auditory brain regions. Tissue blocks containing the medial geniculate body (MGB), thalamic reticular nucleus (TRN), central part of the inferior colliculus (CIC), and dorsal and obscurus raphe nuclei (DRN and ROb) were obtained from tinnitus patients and matched controls. Cell density and size were assessed in Nissl-stained sections. Astrocytes and microglia were assessed using immunohistochemistry. The DRN was stained using antibodies raised against phenylalanine hydroxylase-8 (PH8) and tyrosine-hydroxylase (TH) to visualize serotonergic and dopaminergic cells, respectively. Cell density in the MGB and CIC of tinnitus patients was reduced, accompanied by a reduction in the number of astrocytes in the CIC only. Quantification of cell surface size did not reveal any significant difference in any of the investigated brain regions between groups. The number of PH8-positive cells was reduced in the DRN and ROb of tinnitus patients compared to controls, while the number of TH-positive cells remained unchanged in the DRN. These findings suggest that both neurodegenerative and inflammatory processes in the MGB and CIC underlie the neuropathology of tinnitus. Moreover, the reduced number of serotonergic cell bodies in tinnitus cases points toward a potential role of the raphe serotonergic system in tinnitus.