Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson’s disease

Deep brain stimulation(DBS)is a well-established and effective treatment for patients with advanced Parkinson’s disease(PD),yet its underlying mechanisms remain enigmatic.Optogenetics,primarily conducted in animal models,provides a unique approach that allows cell type-and projection-specific modulation that mirrors the frequency-dependent stimulus effects of DBS.Opto-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD treatment.DBS-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs,frequency-dependent synaptic depression,and the intrinsic excitability of postsynaptic neurons.This orchestration leads to conversion of firing patterns,enabling both antidromic and orthodromic modulation of neural circuits.Understanding these mechanisms is vital for decoding position-and programming-dependent effects of DBS.Furthermore,patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic benefits.Research on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation patterns.Advanced technologies,such as adaptive DBS or directional electrodes,can also be integrated for circuit-specific neuromodulation.These insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.

THE PROJECTION LINKAGE BETWEEN THE SPINAL DORSAL HORN NEURONS AND BOTH THE SOLITARY TRACT AND DORSAL COLUMN NUCLEI

Electrical stimulation of the solitary tract nucleus (SN) and dorsal column nuclei (DCN)as well as microelectrode recording from the lumbal spinal dorsal horn have been used tofind and identify the axonal projection of and the afferent innervation on the spinal neuronsof pentobarbital- anesthetized rats. A total of 92 neurons was recorded and identified mainly in laminae Ⅲ-Ⅴ of the lumbarspinal dorsal horn. Of them, 38 neurons were activated antidromically from stimulation ofboth the SN and DCN. The other 54 neurons responded synaptically to both the SN andDCN stimulations. The initial antidromic responses of 8 neurons in the first group werefollowed by one or more responses synaptically driven from the SN and/or DCN stimulation.Conduction velocities were in the range of A delta fibers, but faster in the antidromicresponses and slower in the synaptic responses. These results indicate that (i) some spinal neurons issue branched axons of larger-sizedA delta fibers and double project to both the SN and DCN; (ii) some of these doubleprojection neurons receive in turn smaller A delta fiber innervation from the SN and/orDCN; and (iii) some other neurons in the spinal cord are dually innervated by smaller Adelta fibers originating from both nuclei.

The Functional Linkage Among the "ZSL"-Spinal Dorsal Horn-SN

Electrical stimulation of the Zusanli point (ZSL) and solitary tract nucleus (SN) as well as microelectrode recording from the laminae Ⅲ-Ⅴ of the lumbar spinal dorsal horn have been used on the pentobarbital anesthetized rats, finding and identifying 57 spinal neurons responding to the stimulations of both ZSL and SN. Among them, 34 responded antidromically to SN; the others responded orthodromically to SN. Among them, the lowthreshold mechano-receptive(LTM) neurons and wide-dynamic-range (WDR) neurons were 50 percent respectively. The results indicate that (ⅰ) a single spinal dorsal horn neuron receives somatic afferent input and then conveys it to the visceral sensory nucleus-SN; (ⅱ) some spinal dorsal horn neurons receive, in turn, innervation from the SN; (ⅲ) the convergence and integration between somatic and visceral sensory inputs might occur in the spinal dorsal horn neurons and/or SN.