Phase-locking of bursting neuronal firing to dominant LFP frequency components

Neuronal firing in the hippocampal formation relative to the phase of local field potentials (LFP) has a key role in memory processing and spatial navigation. Firing can be in either tonic or burst mode. Although bursting neurons are common in the hippocampal formation, the characteristics of their locking to LFP phase are not completely understood. We investigated phase-locking properties of bursting neurons using simulations generated by a dual compartmental model of a pyramidal neuron adapted to match the bursting activity in the subiculum of a rat. The model was driven with stochastic input signals containing a power spectral profile consistent with physiologically relevant frequencies observed in LFP. The single spikes and spike bursts fired by the model were locked to a preferred phase of the predominant frequency band where there was a peak in the power of the driving signal. Moreover, the preferred phase of locking shifted with increasing burst size, providing evidence that LFP phase can be encoded by burst size. We also provide initial support for the model results by analysing example data of spontaneous LFP and spiking activity recorded from the subiculum of a single urethane-anaesthetised rat. Subicular neurons fired single spikes, two-spike bursts and larger bursts that locked to a preferred phase of either dominant slow oscillations or theta rhythms within the LFP, according to the model prediction. Both power-modulated phase-locking and gradual shift in the preferred phase of locking as a function of burst size suggest that neurons can use bursts to encode timing information contained in LFP phase into a spike-count code

Bursting Neurons in the Hippocampal Formation Encode Features of LFP Rhythms

Burst spike patterns are common in regions of the hippocampal formation such as the subiculum and medial entorhinal cortex (MEC). Neurons in these areas are immersed in extracellular electrical potential fluctuations often recorded as the local field potential (LFP). LFP rhythms within different frequency bands are linked to different behavioral states. For example, delta rhythms are often associated with slow-wave sleep, inactivity and anesthesia; whereas theta rhythms are prominent during awake exploratory behavior and REM sleep. Recent evidence suggests that bursting neurons in the hippocampal formation can encode LFP features. We explored this hypothesis using a two-compartment model of a bursting pyramidal neuron driven by time-varying input signals containing spectral peaks at either delta or theta rhythms. The model predicted a neural code in which bursts represented the instantaneous value, phase, slope and amplitude of the driving signal both in their timing and size (spike number). To verify whether this code is employed in vivo, we examined electrophysiological recordings from the subiculum of anesthetized rats and the MEC of a behaving rat containing prevalent delta or theta rhythms, respectively. In both areas, we found bursting cells that encoded information about the instantaneous voltage, phase, slope and/or amplitude of the dominant LFP rhythm with essentially the same neural code as the simulated neurons. A fraction of the cells encoded part of the information in burst size, in agreement with model predictions. These results provide in-vivo evidence that the output of bursting neurons in the mammalian brain is tuned to features of the LFP

Generation of physiological and pathological high frequency oscillations: the role of perisomatic inhibition in sharp-wave ripple and interictal spike generation

Sharp-wave-ripple complexes (SWRs) and interictal-spikes are physiological and pathological forms of irregularly occurring transient high activity events in the hippocampal EEG. They share similar features and carry high-frequency oscillations with different spectral features. Recent results reveal similarities and differences in the generation of the two types of transients, and argue that parvalbumin containing basket cells (PVBCs) are crucial in synchronizing neuronal activity in both cases. SWRs are generated in the reciprocally connected network of inhibitory PVBCs, while in the pathological case, synchronous failure of perisomatic inhibition triggers massive pyramidal cell burst firing. While physiological ripple oscillation is primarily the result of phasic perisomatic inhibitory currents, pathological high-frequency ripples are population spikes of partially synchronous, massively bursting, uninhibited pyramidal cells

Visual cortical alpha rhythms : function and relation to other dynamic signatures in local networks

The alpha rhythm (8-12Hz) was the first EEG rhythm recorded by Hans Berger in 1929. Despite being the earliest rhythm discovered, alpha rhythms remain the most mysterious in terms of mechanism and function. In the visual system, post-stimulus alpha oscillations are observed upon closing of the eyes or removal of visual stimulus. Alpha rhythms have been implicated in functional inhibition and short term memory. This thesis presents a rat in vitro model of the cortical alpha rhythm. This was achieved by mimicking the neuromodulatory changes that occur upon the removal of visual stimulus. Beta oscillations were induced by excitation of the visual cortex slice using the glutamate agonist kainate [800nM] to mimic sensory stimulation. This excitatory drive was then reduced using the AMPA and KA receptor antagonist NBQX [5µM], followed by the blocking of neuronal Ih current with DK-AH269 [10µM] to produce alpha frequency oscillations.Alpha activity was seen throughout all cortical laminae, with alpha power predominating in layer IV of the V1. The rhythm was found to be criticallydependent upon NMDA receptor-mediated connections between neurons which required the need to be potentiated in the prior excitation phase leading to beta frequency oscillations. Alpha activity was also dependent upon gap junctional coupling and had neuromodulatory effects similar to the human profile of alpha.Alpha oscillations were generated by pyramidal neurons found in layer IV of the V1 which elicited burst discharges. The alpha rhythm was not dominated by synaptic inhibition despite the functional inhibition role it is thought to play. Instead, the alpha rhythm appeared to dynamically uncouple activity in the primary thalamorecipient neurons (layer IV regular spiking cells) from down-stream activity in both supragranular and infragranular layers. In this manner, the alpha rhythm appears to be ideally constructed to prevent ascending visual information from both passing on to higher order visual areas, and also being influenced by top-down signal from these areas

Dynamic Control of Network Level Information Processing through Cholinergic Modulation

Acetylcholine (ACh) release is a prominent neurochemical marker of arousal state within the brain. Changes in ACh are associated with changes in neural activity and information processing, though its exact role and the mechanisms through which it acts are unknown. Here I show that the dynamic changes in ACh levels that are associated with arousal state control informational processing functions of networks through its effects on the degree of Spike-Frequency Adaptation (SFA), an activity dependent decrease in excitability, synchronizability, and neuronal resonance displayed by single cells. Using numerical modeling I develop mechanistic explanations for how control of these properties shift network activity from a stable high frequency spiking pattern to a traveling wave of activity. This transition mimics the change in brain dynamics seen between high ACh states, such as waking and Rapid Eye Movement (REM) sleep, and low ACh states such as Non-REM (NREM) sleep. A corresponding, and related, transition in network level memory recall is also occurs as ACh modulates neuronal SFA. When ACh is at its highest levels (waking) all memories are stably recalled, as ACh is decreased (REM) in the model weakly encoded memories destabilize while strong memories remain stable. In levels of ACh that match Slow Wave Sleep (SWS), no encoded memories are stably recalled. This results from a competition between SFA and excitatory input strength and provides a mechanism for neural networks to control the representation of underlying synaptic information. Finally I show that during the low ACh conditions, oscillatory conditions allow for external inputs to be properly stored in and recalled from synaptic weights. Taken together this work demonstrates that dynamic neuromodulation is critical for the regulation of information processing tasks in neural networks. These results suggest that ACh is capable of switching networks between two distinct information processing modes. Rate coding of information is facilitated during high ACh conditions and phase coding of information is facilitated during low ACh conditions. Finally I propose that ACh levels control whether a network is in one of three functional states: (High ACh; Active waking) optimized for encoding of new information or the stable representation of relevant memories, (Mid ACh; resting state or REM) optimized for encoding connections between currently stored memories or searching the catalog of stored memories, and (Low ACh; NREM) optimized for renormalization of synaptic strength and memory consolidation. This work provides a mechanistic insight into the role of dynamic changes in ACh levels for the encoding, consolidation, and maintenance of memories within the brain.PHDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147503/1/roachjp_1.pd

The role of oscillation population activity in cortico-basal ganglia circuits.

The basal ganglia (BG) are a group of subcortical brain nuclei that are anatomically situated between the cortex and thalamus. Hitherto, models of basal ganglia function have been based solely on the anatomical connectivity and changes in the rate of neurons mediated by inhibitory and excitatory neurotransmitter interactions and modulated by dopamine. Depletion of striatal dopamine as occurs in Parkinson's Disease (PD) however, leads primarily to changes in the rhythmicity of basal ganglia neurons. The general aim of this thesis is to use frontal electrocorticogram (ECoG) and basal ganglia local field potential (LFP) recordings in the rat to further investigate the putative role for oscillations and synchronisation in these structures in the healthy and dopamine depleted brain. In the awake animal, lesion of the SNc lead to a dramatic increase in the power and synchronisation of P-frequency band oscillations in the cortex and subthalamic nucleus (STN) compared to the sham lesioned animal. These results are highly similar to those in human patients and provide further evidence for a direct pathophysological role for p-frequency band oscillations in PD. In the healthy, anaesthetised animal, LFPs recorded in the STN, globus pallidus (GP) and substantia nigra pars reticulata (SNr) were all found to be coherent with the ECoG. A detailed analysis of the interdependence and direction of these activities during two different brain states, prominent slow wave activity (SWA) and global activation, lead to the hypothesis that there were state dependant changes in the dominance of the cortico-subthalamic and cortico-striatal pathways. Multiple LFP recordings in the striatum and GP provided further evidence for this hypothesis, as coherence between the ECoG and GP was found to be dependent on the striatum. Together these results suggest that oscillations and synchronisation may mediate information flow in cortico-basal ganglia networks in both health and disease

Neuron-level dynamics of oscillatory network structure and markerless tracking of kinematics during grasping

Oscillatory synchrony is proposed to play an important role in flexible sensory-motor transformations. Thereby, it is assumed that changes in the oscillatory network structure at the level of single neurons lead to flexible information processing. Yet, how the oscillatory network structure at the neuron-level changes with different behavior remains elusive. To address this gap, we examined changes in the fronto-parietal oscillatory network structure at the neuron-level, while monkeys performed a flexible sensory-motor grasping task. We found that neurons formed separate subnetworks in the low frequency and beta bands. The beta subnetwork was active during steady states and the low frequency network during active states of the task, suggesting that both frequencies are mutually exclusive at the neuron-level. Furthermore, both frequency subnetworks reconfigured at the neuron-level for different grip and context conditions, which was mostly lost at any scale larger than neurons in the network. Our results, therefore, suggest that the oscillatory network structure at the neuron-level meets the necessary requirements for the coordination of flexible sensory-motor transformations. Supplementarily, tracking hand kinematics is a crucial experimental requirement to analyze neuronal control of grasp movements. To this end, a 3D markerless, gloveless hand tracking system was developed using computer vision and deep learning techniques. 2021-11-3