Biology subjects

Moghaddam, B.

Publications and source records attributed to Moghaddam, B..

5 recordsLinked to original sources

bioRxiv2018

Dopamine modulation of prefrontal cortex activity is manifold and operates at multiple temporal and spatial scales

While the function of dopamine in subcortical structures is largely limited to reward and movement, dopamine neurotransmission in the prefrontal cortex (PFC) is critical to a multitude of temporally and functionally diverse processes such as attention, working memory, behavioral flexibility, action selection, and stress adaptation. How does dopamine influence PFC computation of multiple temporally diverse functions? Here we find causation between sustained and burst patterns of phasic dopamine neuron activation and contemporaneous modulation of PFC neuronal activity at multiple spatio-temporal scales. These include a multidirectional and weak impact on individual PFC neuron rate activity and a robust influence on coordinated ensemble activity, gamma oscillations, and gamma-theta coupling that persisted for minutes. In addition, PFC network responses to burst pattern of dopamine firing were selectively strengthened in behaviorally active states. Thus, dopamine modulation of PFC is spatiotemporally diverse and is dictated by the pattern of dopamine neuron activation and behavioral state. These findings provide insight on the multiplex pattern of modulation by dopamine that may influence PFC computation of temporally diverse functions.

neuroscience↗

bioRxiv2018

Efficient sorting of single-unit activity from midbrain cells using KiloSort is as accurate as manual sorting.

Extracting single-unit activity from in vivo extracellular neural electrophysiology data requires sorting spikes from background noise and action potentials from multiple cells in order to identify the activity of individual neurons. Typically this has been achieved by algorithms that employ principal component analyses followed by manual allocation of spikes to individual clusters based on visual inspection of the waveform shape. This method of manual sorting can give varying results between human operators and is highly time-consuming, especially in recordings with higher levels of background noise. To address these problems, automatic sorting algorithms have begun to gain popularity as viable methods for sorting electrophysiological data, although little is known about the use of these algorithms with neural data from midbrain recordings. KiloSort is a relatively new algorithm that automatically clusters raw data which can then be manually curated. In this report, we compare results of manually-sorted and KiloSort-processed recordings from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Sorting with KiloSort required substantially less time to complete, while yielding comparable and consistent results. We conclude that the use of KiloSort to identify single units from multi-channel recording in the VTA and SNc is accurate and efficient.

neuroscience↗

bioRxiv2017

Discrete and coordinated encoding of punishment contingent on rewarded actions by prefrontal cortex and VTA

Actions motivated by a rewarding outcome are often associated with a risk of punishment. Little is known about the neural representation of punishment that is contingent on reward-guided behavior. We modeled this circumstance by using a task where actions were consistently rewarded but probabilistically punished. Spike activity and local field potentials were recorded during this task simultaneously from VTA and mPFC, two reciprocally connected regions implicated in both reward-seeking and aversive behavioral states. At the single unit level, we found that ensembles of VTA and mPFC neurons encode the contingency between action and punishment. At the network level, we found that coherent theta oscillations synchronize the VTA and mPFC in a bottom-up direction, effectively phase-modulating the neuronal spike activity in the two regions during punishment-free actions. This synchrony declined as a function of punishment contingency, suggesting that during reward-seeking actions, risk of punishment diminishes VTA-driven neural synchrony between the two regions.

neuroscience↗

bioRxiv2017

Burst Activation Of Dopamine Neurons Produces Prolonged Post-Burst Availability Of Actively Released Dopamine

Both phasic and tonic modes of neurotransmission are implicated in critical functions assigned to dopamine. In learning, for example, sub-second phasic responses of ventral tegmental area (VTA) dopamine neurons to salient events serve as teaching signals, but learning is also interrupted by dopamine antagonists administered minutes after training. Our findings bridge the multiple timescales of dopamine neurotransmission by demonstrating that burst stimulation of VTA dopamine neurons produces a prolonged post-burst increase (> 20 min) of extracellular dopamine in nucleus accumbens and prefrontal cortex. This elevation is not due to spillover from the stimulation surge but depends on impulse flow-mediated dopamine release. We identified Rho-mediated internalization of dopamine transporter as a mechanism responsible for prolonged availability of actively released dopamine. These results demonstrate that phasic and tonic dopamine neurotransmission can be a continuum and may explain why both modes of signaling are critical for motivational and cognitive functions associated with dopamine.

neuroscience↗

bioRxiv2016

Ventral tegmental area neurons use an ensemble code for representing information about ongoing actions

Multiple and unpredictable numbers of actions are often required to achieve a goal. In order to organize behavior and allocate effort so that optimal behavioral policies can be selected, it is necessary to continually monitor ongoing actions. Real-time processing of information related to actions and outcomes is typically assigned to the prefrontal cortex and basal ganglia, but also depends on midbrain regions, especially the ventral tegmental area (VTA). We were interested in how individual VTA neurons, as well as networks within the VTA, encode salient events when an unpredictable number of serial actions are required to obtain a reward. We recorded from ensembles of putative dopamine and non-dopamine neurons in the VTA as animals performed multiple cued trials in a recording session where, in each trial, serial actions were randomly rewarded. While averaging population activity did not reveal a response pattern, we observed that different neurons selectively tuned to low, medium, or high numbered actions in a trial. This preferential tuning of putative dopamine and non-dopamine VTA neurons to different subsets of actions in a trial allowed information about binned action number to be decoded from the ensemble activity. At the network level, tuning curve similarity was positively associated with action-evoked noise correlations, suggesting that action number selectivity reflects functional connectivity within these networks. Analysis of phasic responses to cue and reward revealed that the requirement to execute multiple and uncertain numbers of actions weakens both cue-evoked responses and cue-reward response correlation. The functional connectivity and ensemble coding scheme that we observe here may allow VTA neurons to cooperatively provide a real-time account of ongoing behavior. These computations may be critical to cognitive and motivational functions that have long been associated with VTA dopamine neurons.

neuroscience↗