Cerebellar Coordination of Neuronal Communication in Cerebral Cortex

McAfee, Samuel S.; Liu, Yü; Sillitoe, Roy V.; Heck, Detlef H.

doi:10.3389/fnsys.2021.781527

Cited by 32 publications

(27 citation statements)

References 182 publications

(285 reference statements)

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“…The further development of sophisticated genetic approaches that aim to manipulate the molecular, cellular, and functional properties of the dystonia circuit will enhance experimental possibilities and provide the means to address the many challenges of solving dystonia. In addition, the identification of new behavioral roles of the cerebellum that encompass motor and non-motor domains [75] and existing knowledge of cerebellar-related functional defects in human dystonia patients [76][77][78] highlight an exciting framework to more deeply test how cerebellar circuits impact dystonia. We propose that the complexity of behaviors observed across the different dystonias may be reflected within the extensive connectivity of the cerebellar system.…”

Section: Discussionmentioning

confidence: 99%

Cerebellar Dysfunction as a Source of Dystonic Phenotypes in Mice

et al. 2022

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There is now a substantial amount of compelling evidence demonstrating that the cerebellum may be a central locus in dystonia pathogenesis. Studies using spontaneous genetic mutations in rats and mice, engineered genetic alleles in mice, shRNA knockdown in mice, and conditional genetic silencing of fast neurotransmission in mice have all uncovered a common set of behavioral and electrophysiological defects that point to cerebellar cortical and cerebellar nuclei dysfunction as a source of dystonic phenotypes. Here, we revisit the Ptf1aCre/+;Vglut2flox/flox mutant mouse to define fundamental phenotypes and measures that are valuable for testing the cellular, circuit, and behavioral mechanisms that drive dystonia. In this model, excitatory neurotransmission from climbing fibers is genetically eliminated and, as a consequence, Purkinje cell and cerebellar nuclei firing are altered in vivo, with a prominent and lasting irregular burst pattern of spike activity in cerebellar nuclei neurons. The resulting impact on behavior is that the mice have developmental abnormalities, including twisting of the limbs and torso. These behaviors continue into adulthood along with a tremor, which can be measured with a tremor monitor or EMG. Importantly, expression of dystonic behavior is reduced upon cerebellar-targeted deep brain stimulation. The presence of specific combinations of disease-like features and therapeutic responses could reveal the causative mechanisms of different types of dystonia and related conditions. Ultimately, an emerging theme places cerebellar dysfunction at the center of a broader dystonia brain network.

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Section: Discussionmentioning

confidence: 99%

Cerebellar Dysfunction as a Source of Dystonic Phenotypes in Mice

et al. 2022

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“…In neural systems, analogous informational gating and control mechanisms based on synchronies and oscillations could serve similar functions. Such a role has been proposed for cerebellar coordination of neuronal oscillation coherence in communications across multiple cortical structures ( McAfee et al, 2021 ).…”

Section: Toward An Integrated Systems View Of Brain Functionmentioning

confidence: 99%

“…Flexible coupling of oscillators or neuronal integration in global circuits ( Miller, 2013 ). Recently, a role for the cerebellum in coordinating inter-cortical communications through oscillatory control has been suggested ( McAfee et al, 2021 ). Coherent coupling would also be critical for any heterodyne-like neural mechanisms (§ 8.1.3).…”

Section: Introductionmentioning

confidence: 99%

Time Is of the Essence: Neural Codes, Synchronies, Oscillations, Architectures

Cariani

Baker

2022

Front. Comput. Neurosci.

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Time is of the essence in how neural codes, synchronies, and oscillations might function in encoding, representation, transmission, integration, storage, and retrieval of information in brains. This Hypothesis and Theory article examines observed and possible relations between codes, synchronies, oscillations, and types of neural networks they require. Toward reverse-engineering informational functions in brains, prospective, alternative neural architectures incorporating principles from radio modulation and demodulation, active reverberant circuits, distributed content-addressable memory, signal-signal time-domain correlation and convolution operations, spike-correlation-based holography, and self-organizing, autoencoding anticipatory systems are outlined. Synchronies and oscillations are thought to subserve many possible functions: sensation, perception, action, cognition, motivation, affect, memory, attention, anticipation, and imagination. These include direct involvement in coding attributes of events and objects through phase-locking as well as characteristic patterns of spike latency and oscillatory response. They are thought to be involved in segmentation and binding, working memory, attention, gating and routing of signals, temporal reset mechanisms, inter-regional coordination, time discretization, time-warping transformations, and support for temporal wave-interference based operations. A high level, partial taxonomy of neural codes consists of channel, temporal pattern, and spike latency codes. The functional roles of synchronies and oscillations in candidate neural codes, including oscillatory phase-offset codes, are outlined. Various forms of multiplexing neural signals are considered: time-division, frequency-division, code-division, oscillatory-phase, synchronized channels, oscillatory hierarchies, polychronous ensembles. An expandable, annotative neural spike train framework for encoding low- and high-level attributes of events and objects is proposed. Coding schemes require appropriate neural architectures for their interpretation. Time-delay, oscillatory, wave-interference, synfire chain, polychronous, and neural timing networks are discussed. Some novel concepts for formulating an alternative, more time-centric theory of brain function are discussed. As in radio communication systems, brains can be regarded as networks of dynamic, adaptive transceivers that broadcast and selectively receive multiplexed temporally-patterned pulse signals. These signals enable complex signal interactions that select, reinforce, and bind common subpatterns and create emergent lower dimensional signals that propagate through spreading activation interference networks. If memory traces share the same kind of temporal pattern forms as do active neuronal representations, then distributed, holograph-like content-addressable memories are made possible via temporal pattern resonances.

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“…Along these pathways, cerebellar cortex is organized into parasagittal microzones which project in distinctive patterns, so that lobule VI and crus I make different patterns of disynaptic connectivity with thalamic structures [24][25][26], and trisynaptic paths to anterior cingulate, infralimbic, and somatosensory cortex [1][2][3][4][5]. Each of these cerebellar regions also receives descending input from the neocortex via the pons [27,28] and inferior olive [29]. These cerebellar regions therefore have distinctive routes by which they may influence forebrain processing across many distributed targets.…”

Section: Introductionmentioning

confidence: 99%

Cerebellar contributions to a brainwide network for reversal learning

Verpeut

Bergeler

Kislin

et al. 2021

Preprint

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The cerebellum regulates nonmotor behavior, but the routes by which it exerts its influence are not well characterized. Here we report a necessary role for posterior cerebellum in guiding flexible behavior, acting through a network of diencephalic and neocortical structures. After chemogenetic inhibition of Purkinje cells in lobule VI or crus I, high-throughput automated analysis of complex whole-body movement revealed deficiencies in adaptation across days to an open field environment. Neither perturbation affected gait, within-day open-field adaptation, or location preference. In a Y-maze task, mice could learn but were impaired in their ability to reverse their initial choice. To map targets of perturbation, we imaged c-Fos activation in cleared whole brains using light-sheet microscopy. Reversal learning activated diencephalic regions and associative neocortical regions. Distinctive subsets of structures were altered by perturbation of lobule VI (thalamus and habenula) and crus I (hypothalamus and prelimbic/orbital cortex), and both perturbations influenced anterior cingulate and infralimbic cortex. Taken together, these experiments reveal parts of a brainwide system for cerebellar influence to guide flexible learning.

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Cerebellar Coordination of Neuronal Communication in Cerebral Cortex

Cited by 32 publications

References 182 publications

Cerebellar Dysfunction as a Source of Dystonic Phenotypes in Mice

Cerebellar Dysfunction as a Source of Dystonic Phenotypes in Mice

Time Is of the Essence: Neural Codes, Synchronies, Oscillations, Architectures

Cerebellar contributions to a brainwide network for reversal learning

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