Ross William Anderson

All Publications

• Deep brain stimulation mechanisms: the control of network activity via neurochemistry modulation JOURNAL OF NEUROCHEMISTRY McIntyre, C. C., Anderson, R. W. 2016; 139: 338-345

  Abstract

  Deep brain stimulation (DBS) has revolutionized the clinical care of late-stage Parkinson's disease and shows promise for improving the treatment of intractable neuropsychiatric disorders. However, after over 25 years of clinical experience, numerous questions still remain on the neurophysiological basis for the therapeutic mechanisms of action. At their fundamental core, the general purpose of electrical stimulation therapies in the nervous system are to use the applied electric field to manipulate the opening and closing of voltage-gated sodium channels on neurons, generate stimulation induced action potentials, and subsequently, control the release of neurotransmitters in targeted pathways. Historically, DBS mechanisms research has focused on characterizing the effects of stimulation on neurons and the resulting impact on neuronal network activity. However, when electrodes are placed within the central nervous system, glia are also being directly (and indirectly) influenced by the stimulation. Mounting evidence shows that non-neuronal tissue can play an important role in modulating the neurochemistry changes induced by DBS. The goal of this review is to evaluate how DBS effects on both neuronal and non-neuronal tissue can potentially work together to suppress oscillatory activity (and/or information transfer) between brain regions. These resulting effects of ~ 100 Hz electrical stimulation help explain how DBS can disrupt pathological network activity in the brain and generate therapeutic effects in patients. Deep brain stimulation is an effective clinical technology, but detailed therapeutic mechanisms remain undefined. This review provides an overview of the leading hypotheses, which focus on stimulation-induced disruption of network oscillations and integrates possible roles for non-neuronal tissue in explaining the clinical response to therapeutic stimulation. This article is part of a special issue on Parkinson disease.

  View details for DOI 10.1111/jnc.13649

  View details for Web of Science ID 000385770500022

  View details for PubMedID 27273305

  View details for PubMedCentralID PMC5358920

• Subthreshold Oscillations and Persistent Activity Modulate Spike Output in the Rodent Dentate Gyrus Anderson, R. W. OhioLINK. 2015 140

  Abstract

  It is known that the hippocampus is important in learning, memory and spatial navigation. How it performs these tasks at the cellular level in response to neurotransmitters and oscillations in neural circuitry is poorly understood. To determine the role of subthreshold oscillations and persistent activity in information processing in cellular circuits within the hippocampus, I chose two different methods. First, I used whole cell recordings in rat hippocampal slices in vitro to elucidate the role of cholinergic modulation on hippocampal cells. Cholinergic modulation causes dynamic changes in neuronal circuits through the release of the neurotransmitter acetylcholine. I found that cholinergic modulation within the dentate gyrus increased the excitability of dentate mossy cells but not local interneurons through activation of an M1 receptor. During cholinergic modulation, plateau potentials and persistent activity could be stabilized or completely turned off by inhibitory potentials generated by activation of local interneurons. Second, I used in vivo whole cell recordings in awake head-fixed mice to investigate subthreshold oscillations in dentate gyrus cells to determine their response during animal movement. I found that dentate gyrus neurons demonstrated subthreshold oscillations in the 8-15 Hz frequency band that were initiated near the onset of spontaneous bouts of motion. These oscillations often preceded the movement onset and their strength in the first 2-seconds was largest in movements along the animals natural forward/backward direction. Lastly, the power of this oscillation would predict the duration of time the animal would run. This data suggest that dynamic changes in network excitability as the result of cholinergic release or subthreshold oscillation functions to control the cellular processes responsible for memory formation and spatial navigation.

• alpha-Band oscillations in intracellular membrane potentials of dentate gyrus neurons in awake rodents LEARNING & MEMORY Anderson, R. W., Strowbridge, B. W. 2014; 21 (12): 656-661

  Abstract

  The hippocampus and dentate gyrus play critical roles in processing declarative memories and spatial information. Dentate granule cells, the first relay in the trisynaptic circuit through the hippocampus, exhibit low spontaneous firing rates even during locomotion. Using intracellular recordings from dentate neurons in awake mice operating a levitated spherical treadmill, we found a transient membrane potential α-band oscillation associated with the onset of spontaneous motion, especially forward walking movements. While often subthreshold, α oscillations could regulate spike timing during locomotion and may enable dentate gyrus neurons to respond to specific cortical afferent pathways while maintaining low average firing rates.

  View details for DOI 10.1101/lm.036269.114

  View details for Web of Science ID 000346359500003

  View details for PubMedID 25403453

  View details for PubMedCentralID PMC4236408

• Regulation of persistent activity in hippocampal mossy cells by inhibitory synaptic potentials LEARNING & MEMORY Anderson, R. W., Strowbridge, B. W. 2014; 21 (5): 263-271

  Abstract

  The hippocampal formation receives strong cholinergic input from the septal/diagonal band complex. Although the functional effects of cholinergic activation have been extensively studied in pyramidal neurons within the hippocampus and entorhinal cortex, less is known about the role of cholinergic receptors on dentate gyrus neurons. Using intracellular recordings from rat dentate hilar neurons, we find that activation of m1-type muscarinic receptors selectively increases the excitability of glutamatergic mossy cells but not of hilar interneurons. Following brief stimuli, cholinergic modulation reveals a latent afterdepolarization response in mossy cells that can extend the duration of stimulus-evoked depolarization by >100 msec. Depolarizing stimuli also could trigger persistent firing in mossy cells exposed to carbachol or an m1 receptor agonist. Evoked IPSPs attenuated the ADP response in mossy cells. The functional effect of IPSPs was amplified during ADP responses triggered in the presence of cholinergic receptor agonists but not during slowly decaying simulated ADPs, suggesting that modulation of ADP responses by IPSPs arises from destabilization of the intrinsic currents underlying the ADP. Evoked IPSPs also could halt persistent firing triggered by depolarizing stimuli. These results show that through intrinsic properties modulated by muscarinic receptors, mossy cells can prolong depolarizing responses to excitatory input and extend the time window where multiple synaptic inputs can summate. By actively regulating the intrinsic response to synaptic input, inhibitory synaptic input can dynamically control the integration window that enables detection of coincident inputs and shape the spatial pattern of hilar cell activity.

  View details for DOI 10.1101/lm.033829.113

  View details for Web of Science ID 000338505300003

  View details for PubMedID 24737918

  View details for PubMedCentralID PMC3994498

• Analysis of N-15-H-1 NMR Relaxation in Proteins by a Combined Experimental and Molecular Dynamics Simulation Approach: Picosecond-Nanosecond Dynamics of the Rho GTPase Binding Domain of Plexin-B1 in the Dimeric State Indicates Allosteric Pathways JOURNAL OF PHYSICAL CHEMISTRY B Zerbetto, M., Anderson, R., Bouguet-Bonnet, S., Rech, M., Zhang, L., Meirovitch, E., Polimeno, A., Buck, M. 2013; 117 (1): 174-184

  Abstract

  We investigate picosecond–nanosecond dynamics of the Rho-GTPase Binding Domain (RBD) of plexin-B1, which plays a key role in plexin-mediated cell signaling. Backbone 15N relaxation data of the dimeric RBD are analyzed with the model-free (MF) method, and with the slowly relaxing local structure/molecular dynamics (SRLS-MD) approach. Independent analysis of the MD trajectories, based on the MF paradigm, is also carried out. MF is a widely popular and simple method, SRLS is a general approach, and SRLS-MD is an integrated approach we developed recently. Corresponding parameters from the RBD dimer, a previously studied RBD monomer mutant, and the previously studied complex of the latter with the GTPase Rac1, are compared. The L2, L3, and L4 loops of the plexin-B1 RBD are involved in interactions with other plexin domains, GTPase binding, and RBD dimerization, respectively. Peptide groups in the loops of both the monomeric and dimeric RBD are found to experience weak and moderately asymmetric local ordering centered approximately at the C(i–1)(α)–C(i)(α) axes, and nanosecond backbone motion. Peptide groups in the α-helices and the β-strands of the dimer (the β-strands of the monomer) experience strong and highly asymmetric local ordering centered approximately at the C(i–1)(α)–C(i)(α) axes (N–H bonds). N–H fluctuations occur on the picosecond time scale. An allosteric pathway for GTPase binding, providing new insights into plexin function, is delineated.

  View details for DOI 10.1021/jp310142f

  View details for Web of Science ID 000313220600019

  View details for PubMedID 23214953

  View details for PubMedCentralID PMC3556999