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Masmanidis, S. C.

Publications and source records attributed to Masmanidis, S. C..

8 recordsLinked to original sources

Learning dynamically regulates stimulus discrimination of ventral striatal D1 receptor expressing neurons

Animals encounter a barrage of sensory stimuli, but only a subset of these are associated with appetitive outcomes, highlighting the importance of neural mechanisms for learning to distinguish reward-paired from unpaired cues. The ventral striatum plays a critical role in both reinforcement learning and stimulus discrimination, but the effect of learning on the selectivity of different cell types remains unclear. Here we examined ventral striatal D1 and D2 medium spiny neuron (MSN) firing properties as mice learned to distinguish between reward-paired and unpaired cues. As learning progressed within a single session, D1 MSN selectivity increased linearly with behavioral selectivity, while D2 MSNs exhibited only modest, behaviorally uncorrelated changes in activity. Altered D1 MSN selectivity was primarily attributed to attenuated excitatory responses to the unrewarded cue, and increasing D1 MSN activity during the unrewarded cue impaired behavioral selectivity. Together, these findings reveal significantly more dynamic contributions of D1 MSNs to stimulus discrimination learning.

neuroscience↗

Complementary cortical and striatal encoding of locomotor preparation and performance

Cortical and striatal circuits play an important role in motor planning and execution, and encode movement-related information. While neural dynamics in these areas show substantial similarities, possibly reflecting shared information content, studies directly comparing the cortical and striatal encoding of locomotor preparation and performance have been lacking. Here we contrasted the neural coding properties of mouse primary motor and medial prefrontal cortex, as well as dorsolateral and dorsomedial striatum, prior to and during bouts of self-initiated walking. All four areas contained cells active during both the preparatory and performance periods of locomotion. However, the decoding of behaviorally relevant information using population-level activity revealed significant regional variations. Specifically, dorsomedial striatum more accurately encoded the preparatory period prior to walking, while primary motor cortex more accurately encoded rhythmic limb kinematics during walking. Together, this work provides evidence for a complementary neural coding scheme for locomotor preparation and performance in cortical and striatal circuits.

neuroscience↗

Dopamine lesions alter the striatal encoding of single-limb gait

The striatum an important role in motor control, and neurons in this area encode the bodys initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking in D2 MSNs. These findings indicate that striatal neurons represent gait on a single-limb and step basis, and suggest that elevated limb phase-locking of D2 MSNs may underlie some of the gait impairments associated with dopamine loss.

neuroscience↗

Correlated signatures of social behavior in cerebellum and anterior cingulate cortex

The cerebellum has been implicated in the regulation of social behavior. Its influence is thought to arise from communication, via the thalamus, to forebrain regions integral in the expression of social interactions, including the anterior cingulate cortex (ACC). However, the signals encoded or the nature of the communication between the cerebellum and these brain regions is poorly understood. Here, we describe an approach that overcomes technical challenges in exploring the coordination of distant brain regions at high temporal and spatial resolution during social behavior. We developed the E-Scope, an electrophysiology-integrated miniature microscope, to synchronously measure extracellular electrical activity in the cerebellum along with calcium imaging of the ACC. This single coaxial cable device combined these data streams to provide a powerful tool to monitor the activity of distant brain regions in freely behaving animals. During social behavior, we recorded the spike timing of multiple single units in cerebellar right Crus I (RCrus I) Purkinje cells (PCs) or dentate nucleus (DN) neurons while synchronously imaging calcium transients in contralateral ACC neurons. We found that during social interactions a significant subpopulation of cerebellar PCs were robustly inhibited, while most modulated neurons in the DN were activated, and their activity was correlated with positively modulated ACC neurons. These distinctions largely disappeared when only non-social epochs were analyzed suggesting that cerebellar-cortical interactions were behaviorally specific. Our work provides new insights into the complexity of cerebellar activation and co-modulation of the ACC during social behavior and a valuable open-source tool for simultaneous, multimodal recordings in freely behaving mice.

neuroscience↗

Physiological constraints on the rapid dopaminergic modulation of striatal reward activity

While the contribution of dopaminergic (DA) neurons to associative learning is firmly established, their importance for influencing imminent behavior on short (subsecond) timescales is less clear. Mechanistically, it is thought that DA neurons drive these behavioral changes because of their ability to rapidly alter striatal spiking activity. However, due to limitations of previous approaches, the straightforward prediction that striatal spiking is rapidly influenced by physiologically relevant DA signals has not been rigorously tested. Here, we monitored changes in spiking responses in the ventral striatum while transiently reducing or increasing DA levels. Contrary to the predicted effect, neither spontaneous nor reward-evoked striatal spiking activity was strongly influenced by optogenetic manipulations, except when DA exceeded reward-matched levels. These findings challenge the view that DA plays a major role in rapidly influencing striatal activity. Finally, they suggest a need to distinguish between the modulatory functions of DA under physiological and supra-physiological conditions.

neuroscience↗

Encoding time in neural dynamic regimes with distinct computational tradeoffs

Converging evidence suggests the brain encodes time in time-varying patterns of neural activity, including neural sequences, ramping activity, and complex dynamics. Temporal tasks that require producing the same time-dependent output patterns may have distinct computational requirements in regard to the need to exhibit temporal scaling or generalize to novel contexts. It is not known how neural circuits can both encode time and satisfy distinct computational and generalization requirements, it is also not known whether similar patterns of neural activity at the population level can emerge from distinctly different network configurations. To begin to answer these questions, we trained RNNs on two timing tasks based on behavioral studies. The tasks had different input structures but required producing identically timed output patterns. Using a novel framework we quantified whether RNNs encoded two intervals using either of three different timing strategies: scaling, absolute, or stimulus-specific dynamics. We found that similar neural dynamics for single intervals were associated with fundamentally different encoding strategies and network configurations. Critically, some regimes were better suited for generalization, categorical timing, or robustness to noise. Further analysis revealed different connection patterns underlying the different encoding strategies. Our results predict that apparently similar neural dynamic regimes at the population level can be produced through fundamentally different mechanisms--e.g., in regard to network connectivity and the role of excitatory and inhibitory neurons. We also predict that the task structure used in different experimental studies accounts for some of the experimentally observed variability in how networks encode time. Author summaryThe ability to tell time and anticipate when external events will occur are among the most fundamental computations the brain performs. Converging evidence suggests the brain encodes time through changing patterns of neural activity. Different temporal tasks, however, have distinct computational requirements, such as the need to flexibly scale temporal patterns or generalize to novel inputs. To understand how networks can encode time and satisfy different computational requirements we trained recurrent neural networks (RNNs) on two timing tasks that have previously been used in behavioral studies. Both tasks required producing identically timed output patterns. Using a novel framework to quantify how networks encode different intervals, we found that similar patterns of neural activity--neural sequences--were associated with fundamentally different underlying mechanisms, including the connectivity patterns of the RNNs. Critically, depending on the task the RNNs were trained on, they were better suited for generalization, categorical timing, or robustness to noise. Our results predict that similar patterns of neural activity can be produced by distinct RNN configurations, which in turn have fundamentally different computational tradeoffs. Our results also predict that differences in task structure account for some of the experimentally observed variability in how networks encode time.

neuroscience↗

Inhibition-Dominated Rich-Club Shapes Dynamics in Cortical Microcircuits of Awake Behaving Mice

Functional networks of cortical neurons contain highly interconnected hubs, forming a rich-club structure. However, the cell type composition within this distinct subnetwork and how it influences large-scale network dynamics is unclear. Using spontaneous activity recorded from hundreds of cortical neurons in orbitofrontal cortex of awake behaving mice and from organotypic cultures, we show that the rich-club is disproportionately composed of inhibitory neurons, and that inhibitory neurons within the rich-club are significantly more synchronous than other neurons. At the population level, neurons in the rich-club exert higher than expected Granger causal influence on overall population activity at a broad range of frequencies compared to other neurons. Finally, neuronal avalanche duration is significantly correlated with the fraction of rich neurons that participate in the avalanche. Together, these results suggest an unexpected role of a highly connected, inhibition-rich subnetwork in driving and sustaining activity in local cortical networks. SIGNIFICANCE STATEMENTIt is widely believed that the relative abundance of excitatory and inhibitory neurons in cortical circuits is roughly 4:1. This relative abundance has been widely used to construct numerous cortical network models. Here we show that contrary to this notion, a sub-network of highly connected hub neurons (rich-club) consists of a higher abundance of inhibitory neurons compared to that found in the entire network or the non-rich subnetwork. Inhibitory hub neurons contribute to higher synchrony within the rich club compared to the rest of the network. Strikingly, higher activation of the inhibition-dominated rich club strongly correlates with longer avalanches in cortical circuits. Our findings reveal how network topology combined with cell-type specificity orchestrates population wide activity in cortical microcircuits.

neuroscience↗

DOWN state in the anterior cingulate and prelimbic areas in rats during immobility.

BackgroundUP-DOWN state is considering as a dominant electrographic pattern during immobility and slow wave sleep. This study is focused on the analysis of spatial distribution and neuronal correlates of the DOWN state in rats MethodsLocal field potentials and multiunit discharges were recorded bilaterally in the prefrontal cortex (PFC) and hippocampus of non-anesthetized, tethered rats (Sprague Dawley, males, weight 350-400g) with 256 channel, 4 shank silicon probes. We have focused our study on the analysis of the positive wave of slow oscillations (SOs), which is considered as the DOWN (silent) state of the UP-DOWN state in the anterior cingulate (AC), prelimbic (PL) areas of PFC and hippocampus during immobility. ResultsOur experiments showed that SOs occurred intermittently with a mean interval 1.4{+/-}0.8 ({+/-}SD) seconds. The SOs began with the DOWN state, and they were generated locally within AC or PL areas, or simultaneously in AC, PL and hippocampus bilaterally (generalized SOs). The DOWN state of local SOs in the AC was associated with a decreased rate of multiunit discharges. Similar waves in the PL area were associated with increased multiunit discharges. We observed high speed propagation of generalized SOs that occurred with 3-6ms delay within left and right PFC and less than 10ms delay between the PFC and CA1 area of hippocampus. All generalized SOs were associated with decreased multiunit discharges. ConclusionOur data support the hypothesis that neocortical networks are sufficient to generate focal SOs but the participation of external input is needed for occurrence of generalized SOs.

neuroscience↗