Animals flexibly select actions that maximize future rewards despite facing uncertainty in sen-
sory inputs, action-outcome associations or contexts. The computational and circuit mechanisms
underlying this ability are poorly understood.
A clue to such computations can be found in the neural systems involved in representing sensory
features, sensorimotor-outcome associations and contexts. Specifically, the basal ganglia (BG) have
been implicated in forming sensorimotor-outcome association [1] while the thalamocortical loop
between the prefrontal cortex (PFC) and mediodorsal thalamus (MD) has been shown to engage in
contextual representations [2, 3]. Interestingly, both human and non-human animal experiments
indicate that the MD represents different forms of uncertainty [3, 4]. However, finding evidence
for uncertainty representation gives little insight into how it is utilized to drive behavior.
Normative theories have excelled at providing such computational insights. For example, de-
ploying traditional machine learning algorithms to fit human decision-making behavior has clarified
how associative uncertainty alters exploratory behavior [5, 6]. However, despite their computa-
tional insight and ability to fit behaviors, normative models cannot be directly related to neural
mechanisms. Therefore, a critical gap exists between what we know about the neural representa-
tion of uncertainty on one end and the computational functions uncertainty serves in cognition.
This gap can be filled with mechanistic neural models that can approximate normative models as
well as generate experimentally observed neural representations.
In this work, we build a mechanistic cortico-thalamo-BG loop network model that directly
fills this gap. The model includes computationally-relevant mechanistic details of both BG and
thalamocortical circuits such as distributional activities of dopamine [7] and thalamocortical pro-
jection modulating cortical effective connectivity [3] and plasticity [8] via interneurons. We show
that our network can more efficiently and flexibly explore various environments compared to com-
monly used machine learning algorithms and we show that the mechanistic features we include
are crucial for handling different types of uncertainty in decision-making. Furthermore, through
derivation and mathematical proofs, we approximate our models to two novel normative theories.
We show mathematically the first has near-optimal performance on bandit tasks. The second is
a generalization on the well-known CUMSUM algorithm, which is known to be optimal on single
change point detection tasks [9]. Our normative model expands on this by detecting multiple
sequential contextual changes. To our knowledge, our work is the first to link computational in-
sights, normative models and neural realization together in decision-making under various forms
of uncertainty.
more »
« less
Dopamine Modulation of Motor and Sensory Cortical Plasticity among Vertebrates
Synopsis Goal-directed learning is a key contributor to evolutionary fitness in animals. The neural mechanisms that mediate learning often involve the neuromodulator dopamine. In higher order cortical regions, most of what is known about dopamine’s role is derived from brain regions involved in motivation and decision-making, while significantly less is known about dopamine’s potential role in motor and/or sensory brain regions to guide performance. Research on rodents and primates represents over 95% of publications in the field, while little beyond basic anatomy is known in other vertebrate groups. This significantly limits our general understanding of how dopamine signaling systems have evolved as organisms adapt to their environments. This review takes a pan-vertebrate view of the literature on the role of dopamine in motor/sensory cortical regions, highlighting, when available, research on non-mammalian vertebrates. We provide a broad perspective on dopamine function and emphasize that dopamine-induced plasticity mechanisms are widespread across all cortical systems and associated with motor and sensory adaptations. The available evidence illustrates that there is a strong anatomical basis—dopamine fibers and receptor distributions—to hypothesize that pallial dopamine effects are widespread among vertebrates. Continued research progress in non-mammalian species will be crucial to further our understanding of how the dopamine system evolved to shape the diverse array of brain structures and behaviors among the vertebrate lineage.
more »
« less
- Award ID(s):
- 2035226
- NSF-PAR ID:
- 10312600
- Date Published:
- Journal Name:
- Integrative and Comparative Biology
- Volume:
- 61
- Issue:
- 1
- ISSN:
- 1540-7063
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Synopsis Across the animal kingdom, the ability to produce communication signals appropriate to social encounters is essential, but how these behaviors are selected and adjusted in a context-dependent manner are poorly understood. This question can be addressed on many levels, including sensory processing by peripheral organs and the central nervous system, sensorimotor integration in decision-making brain regions, and motor circuit activation and modulation. Because neuromodulator systems act at each of these levels, they are a useful lens through which to explore the mechanisms underlying complex patterns of communication. It has been clear for decades that understanding the logic of input–output decision making by the nervous system requires far more than simply identifying the connections linking sensory organs to motor circuits; this is due in part to the fact that neuromodulators can promote distinct and temporally dynamic responses to similar signals. We focus on the vocal circuit dynamics of Xenopus frogs, and describe complementary examples from diverse vertebrate communication systems. While much remains to be discovered about how neuromodulators direct flexibility in communication behaviors, these examples illustrate that several neuromodulators can act upon the same circuit at multiple levels of control, and that the functional consequence of neuromodulation can depend on species-specific factors as well as dynamic organismal characteristics like internal state.more » « less
-
more » « less
Activity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, it has been investigated using deprivation approaches in animal models primarily in sensory cortices. Nevertheless, emerging evidence emphasizes its significance in sensory organs and in sub-cortical regions where cranial nerves relay information to the brain. Additionally, critical questions started to arise. Do different sensory modalities share common cellular mechanisms for deprivation-induced plasticity at these central entry-points? Does the deprivation duration correlate with specific plasticity mechanisms?
This study systematically reviews and meta-analyses research papers that investigated visual, auditory, or olfactory deprivation in rodents of both sexes. It examines the consequences of sensory deprivation in homologous regions at the first central synapse following cranial nerve transmission (vision-lateral geniculate nucleus and superior colliculus; audition-ventral and dorsal cochlear nucleus; olfaction-olfactory bulb). The systematic search yielded 91 papers (39 vision, 22 audition, 30 olfaction), revealing substantial heterogeneity in publication trends, experimental methods, measures of plasticity, and reporting across the sensory modalities. Despite these differences, commonalities emerged when correlating plasticity mechanisms with the duration of sensory deprivation. Short-term deprivation (up to 1 day) reduced activity and increased disinhibition, medium-term deprivation (1 day to a week) involved glial changes and synaptic remodelling, and long-term deprivation (over a week) primarily led to structural alterations.
These findings underscore the importance of standardizing methodologies and reporting practices. Additionally, they highlight the value of cross-modals synthesis for understanding how the nervous system, including peripheral, pre-cortical, and cortical areas, respond to and compensate for sensory inputs loss.
Significance Statement This study addresses the critical issue of sensory loss and its impact on the brain's adaptability, shedding light on how different sensory systems respond to loss of inputs from the environment. While past research has primarily explored early-life sensory deprivation, this study focuses on the effects of sensory loss in post-weaning rodents. By systematically reviewing 91 research articles, the findings reveal distinct responses based on the duration of sensory deprivation. This research not only enhances our understanding of brain plasticity but also has broad implications for translational applications, particularly in cross-modal plasticity, offering valuable insights into neuroscientific research and potential clinical interventions. -
more » « less
Abstract Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate movements. In vertebrates, the molecular identities of the cardinal MN types such as those innervating limb versus trunk muscles are well elucidated. Yet the identities of finer subtypes within these cell populations that innervate individual muscle groups remain enigmatic. Here we investigate heterogeneity in mouse MNs using single-cell transcriptomics. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. Additionally, we uncover that axial MNs are subdivided into three molecularly distinct subtypes, defined by mediolaterally-biased Satb2, Nr2f2 or Bcl11b expression patterns with different axon guidance signatures. These three subtypes are present in chicken and human embryos, suggesting a conserved axial MN expression pattern across higher vertebrates. Overall, our study provides a molecular resource of spinal MN types and paves the way towards deciphering how neuronal subtypes evolved to accommodate vertebrate motor behaviors.
-
null (Ed.)Social status-dependent modulation of neural circuits has been investigated extensively in vertebrate and invertebrate systems. However, the effects of social status on neuromodulatory systems that drive motor activity are poorly understood. Zebrafish form a stable social relationship that consists of socially dominant and subordinate animals. The locomotor behavior patterns differ according to their social ranks. The sensitivity of the Mauthner startle escape response in subordinates increases compared to dominants while dominants increase their swimming frequency compared to subordinates. Here, we investigated the role of the endocannabinoid system (ECS) in mediating these differences in motor activities. We show that brain gene expression of key ECS protein pathways are socially regulated. Diacylglycerol lipase (DAGL) expression significantly increased in dominants and significantly decreased in subordinates relative to controls. Moreover, brain gene expression of the cannabinoid 1 receptor (CB 1 R) was significantly increased in subordinates relative to controls. Secondly, increasing ECS activity with JZL184 reversed swimming activity patterns in dominant and subordinate animals. JZL184 did not affect the sensitivity of the startle escape response in dominants while it was significantly reduced in subordinates. Thirdly, blockage of CB 1 R function with AM-251 had no effect on dominants startle escape response sensitivity, but startle sensitivity was significantly reduced in subordinates. Additionally, AM-251 did not affect swimming activities in either social phenotypes. Fourthly, we demonstrate that the effects of ECS modulation of the startle escape circuit is mediated via the dopaminergic system specifically via the dopamine D1 receptor. Finally, our empirical results complemented with neurocomputational modeling suggest that social status influences the ECS to regulate the balance in synaptic strength between excitatory and inhibitory inputs to control the excitability of motor behaviors. Collectively, this study provides new insights of how social factors impact nervous system function to reconfigure the synergistic interactions of neuromodulatory pathways to optimize motor output.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/icb/icab019
