Toms, J. | bioRxiv Science

bioRxiv2024

Deep Brain Stimulation of Nucleus Basalis of Meynert improves learning in rat model of dementia.

BackgroundDeep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been preliminarily investigated as a potential treatment for dementia. The degeneration of NBM cholinergic neurons is a pathological feature of many forms of dementia. Although stimulation of the NBM has been demonstrated to improve learning, the ideal parameters for NBM stimulation have not been elucidated. This study assesses the differential effects of varying stimulation patterns and duration on learning in a dementia rat model. Methods192-IgG-saporin (or vehicle) was injected into the NBM to produce dementia in rats. Next, all rats underwent unilateral implantation of a DBS electrode in the NBM. The experimental groups consisted of i-normal, ii-untreated demented, and iii-demented rats receiving NBM DBS. The stimulation paradigms included testing different modes (tonic and burst) and durations (1-hr, 5-hrs, and 24-hrs/day) over 10 daily sessions. Memory was assessed pre- and post-stimulation using two established learning paradigms: novel object recognition (NOR) and auditory operant chamber learning. ResultsBoth normal and stimulated rats demonstrated improved performance in NOR and auditory learning as compared to the unstimulated demented group. The burst stimulation groups performed better than the tonic stimulated group. Increasing the daily stimulation duration to 24-hr did not further improve cognitive performance in an auditory recognition task and degraded the results on a NOR task as compared with 5-hr. ConclusionThe present findings suggest that naturalistic NBM burst DBS may offer a potential effective therapy for treating dementia and suggests potential strategies for the reevaluation of current human NBM stimulation paradigms.

animal behavior and cognition↗

bioRxiv2019

A Computational Model of Thalamic Tonic-burst Motor Projection Neurons and Their Regulation by Pallidal GABAergic Neurons

A modified computational model of pallidal receiving ventral oral posterior (Vop) thalamocortical motor relay neurons was adapted based on in vivo observations in our rodent model. The model accounts for different input neuronal firing patterns in the primary motor output nucleus of basal ganglia, the globus pallidus interna (GPi) and subsequently generate Vop outputs as observed in vivo under different conditions. Hyperpolarizing input de-inactivates its T-type calcium channel and sets the thalamic neurons in the preferable burst firing mode over a tonic mode and induces low threshold spikes (LTS). In the hyperpolarized state, both spontaneously and in response to excitatory (e.g. corticothalamic) inputs, burst spiking occurs on the crest of the LTS. By selecting and determining the timing and extent of opening of thalamic T-type calcium channels via GABAergic hyperpolarizing input, the GPi precisely regulates Vop-cortical burst motor signaling. Different combinations of tonic, burst, irregular tonic and irregular burst inputs from GPi were used to verify our model. In vivo data obtained from recordings in the entopedunucular nucleus (EP; rodent equivalent of GPi) from resting head restrained healthy and dystonic rats were used to simulate the influences of different inputs from GPi. In all cases, GPi neuronal firing patterns are demonstrated to act as a firing mode selector for thalamic Vop neurons.

neuroscience↗