Biology subjects

Chadderton, P.

Publications and source records attributed to Chadderton, P..

4 recordsLinked to original sources

bioRxiv2023

Cerebellar state estimation enables resilient coupling across behavioural domains

Cerebellar computations are necessary for fine behavioural control and are thought to rely on internal probabilistic models performing state estimation. We propose that the cerebellum infers how states contextualise (i.e., interact with) each other, and coordinates extra-cerebellar neuronal dynamics underpinning a range of behaviours. To support this claim, we describe a cerebellar model for state estimation that includes states interactions, and link the underlying inference with the neuronal architecture and dynamics observed empirically. This is formalised using the free energy principle, which provides a dual perspective on a system in terms of both the dynamics of its physical - in this case neuronal - states, and the inference process they entail. As a proof of principle, we simulate cerebellar-dependent synchronisation of whisking and respiration, which are known to be tightly coupled in rodents. In summary, we suggest that cerebellar-dependent contextualisation of behaviour can explain its ubiquitous involvement in most aspects of behaviour.

neuroscience↗

bioRxiv2022

Cerebellar-driven cortical dynamics enable task acquisition, switching and consolidation

To drive behavior, the cortex must bridge sensory cues with future outcomes. However, the principles by which cortical networks learn such sensory-behavioural transformations remain largely elusive. Here, we posit that the cerebellum assumes a crucial role in driving cortical dynamics, thereby enabling rapid and flexible task acquisition. We introduce a computational model of cerebellar networks which learn to drive cortical networks with task-outcome predictions. First, using sensorimotor tasks we show that cerebellar feedback in the presence of minimal cortical plasticity is suffcient for rapid task acquisition and multiple task switching. Next, we demonstrate that, when trained in working memory tasks, the cerebellum can also underlie the maintenance of cognitive-specific dynamics, explaining a range of optogenetic and behavioural observations. Finally, using our model we introduce a systems consolidation theory in which task information is gradually transferred from the cerebellum to the cortex. In summary, our findings suggest that cortico-cerebellar loops play a pivotal role in task acquisition, switching, and consolidation within the brain.

neuroscience↗

bioRxiv2022

Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice

We studied how co-release of histamine/GABA from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influences circuit processing. We opto-stimulated histamine/GABA co-release from genetically defined TMN axons that express the histidine decarboxylase gene (TMNHDC axons). Whole-cell recordings were used to monitor excitability of visually identified PFC neurons in layer 2/3 of prelimbic (PL), anterior cingulate (AC) and infralimbic (IL) regions before and after opto-stimulated histamine/GABA release. We found that histamine-GABA co-release influences the PFC through actions on distinct neuronal types: histamine stimulates fast-spiking interneurons; and co-released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast spiking non-accommodating interneurons, opto-stimulation increased excitability, an effect blocked by histamine H1 and H2 receptor antagonists. The excitability of other interneuron types in the PFC was not altered. In contrast, the combined action of histamine and GABA co-release from TMNHDC axons produced predominantly divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input-output relationship. The direct inhibitory effect of TMNHDC axon activation on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAA receptor antagonists. Across the adult lifespan (from 3 months to over 2 years of age), stimulation of TMNHDC axons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals that maintain cognitive performance into later life, increases in TMNHDC modulation of PyrNs could enhance information processing and be an adaptive mechanism to buttress cognition.

neuroscience↗

bioRxiv2022

Cerebro-cerebellar networks facilitate learning through feedback decoupling

Behavioural feedback is critical for learning in the cerebral cortex. However, such feedback is often not readily available. How the cerebral cortex learns efficiently despite the sparse nature of feedback remains unclear. Inspired by recent deep learning algorithms, we introduce a systems-level computational model of cerebro-cerebellar interactions. In this model a cerebral recurrent network receives feedback predictions from a cerebellar network, thereby decoupling learning in cerebral networks from future feedback. When trained in a simple sensorimotor task the model shows faster learning and reduced dysmetria-like behaviours, in line with the widely observed functional impact of the cerebellum. Next, we demonstrate that these results generalise to more complex motor and cognitive tasks. Finally, the model makes several experimentally testable predictions regarding (1) cerebro-cerebellar task-specific representations over learning, (2) task-specific benefits of cerebellar predictions and (3) the differential impact of cerebellar and inferior olive lesions. Overall, our work offers a theoretical framework of cerebro-cerebellar networks as feedback decoupling machines.

neuroscience↗