Biology subjects

Broersen, R.

Publications and source records attributed to Broersen, R..

6 recordsLinked to original sources

bioRxiv2026

Electrophysiological properties of mesodiencephalic junction neurons projecting to the inferior olive

Neocortex has the largest volume, while cerebellar cortex houses most neurons of the mammalian brain, underscoring paramount functions for interactions between them. Neocortex projects to the cerebellum via both the mossy fibre and climbing fibre system; whereas the mossy fibres find their origin in the pons, the climbing fibres are relayed via the subnuclei of the inferior olive (IO) that receive their cortical input from the mesodiencephalic junction (MDJ). Since climbing fibres regulate cerebellar plasticity in a timing-dependent manner, the MDJ-IO pathway probably contributes to both sensorimotor and cognitive learning. However, the physiological properties of IO-projecting MDJ neurons remain largely unknown. Here, we made targeted whole-cell recordings in acute brain slices of the murine MDJ, separating IO- from non-IO-projecting neurons following retrograde tracing. We show that IO-projecting neurons are spontaneously active and are capable of high frequency-bursts up to 350 Hz during current injections. Action potentials of IO-projecting MDJ neurons depolarize and re-polarize quickly, and hyperpolarizing inputs consistently trigger rebound action potentials upon stimulus offset. Instead, non-IO-projecting neurons in the same MDJ region are hardly spontaneously active with little rebound activation. Even so, IO-projecting MDJ neurons can also transform excitatory and inhibitory inputs into a proportional output, indicating that they can also employ rate coding. Moreover, neocortical inputs to IO-projecting MDJ neurons can directly be integrated with their inputs from the cerebellar nuclei. Our results highlight how neocortical inputs to the MDJ can be transformed into diverse IO firing patterns and thereby contribute to the required specifics of cerebellar learning. Key points summaryO_LIThe timing of complex spikes in cerebellar Purkinje cells is essential for cerebellar motor learning and proper timing is achieved through the modulation of activity in the inferior olive, the source of all climbing fibres. C_LIO_LIA major source of excitatory input to the inferior olive is the mesodiencephalic junction. C_LIO_LIWe find that that mesodiencephalic junction neurons projecting to the inferior olive represent a population of physiologically distinct neurons, capable of high firing frequencies and rebound activity following inhibition. C_LIO_LIWe reveal how mesodiencephalic junction neurons process excitatory inputs from the neocortex and cerebellar nuclei, as well as inhibitory inputs, enabling mesodiencephalic junction neurons to bidirectionally regulate their activity. C_LIO_LIThese findings shed light on how the inferior olive, critical for cerebellar motor learning, is controlled by the mesodiencephalic junction. C_LI

neuroscience↗

bioRxiv2024

Binocular processing facilitates escape behavior through multiple pathways to the superior colliculus

The superior colliculus (SC) is the main brain region regulating innate defensive behaviors to visual threat. Yet, how the SC integrates binocular visual information and to what extent binocular vision drives defensive behaviors is unknown. Here, we show that binocular vision facilitates visually-evoked escape behavior. Furthermore, we find that SC neurons respond to binocular visual input with diverse synaptic and spiking responses, and summate visual inputs largely sublinearly. Using pathway-specific optogenetic silencing we find that contralateral and ipsilateral visual information is carried to binocular SC neurons through retinal, interhemispheric and corticotectal pathways. These pathways carry binocular visual input to the SC in a layer-specific manner, with superficial layers receiving visual information through retinal input, whereas intermediate and deep layers rely on interhemispheric and corticotectal pathways. Together, our data shed light on the cellular and circuit mechanisms underlying binocular visual processing in the SC and its role in escape behavior.

neuroscience↗

bioRxiv2024

Cellular and circuit mechanisms underlying binocular vision

How binocular visual information is combined at the level of single neurons in the brain is not fully understood. Here, we show in mice that callosal input from the opposite visual cortex (V1) plays a critical role in this process. In vivo we find this callosal projection carries ipsilateral eye information and synapses exclusively onto binocular neurons. Using the presence of callosal input to identify binocular neurons in vitro, at the cellular level we show that binocular neurons are less excitable than monocular neurons due to high expression of Kv1 potassium channels. At the circuit level we find that only monocular neurons send callosal projections to the opposite V1, whereas binocular neurons do not. Finally, using dual-colour optogenetics we show that most binocular and monocular neurons receive direct input from the thalamus. In summary, we describe distinct cellular and circuit mechanisms underlying processing of binocular visual information in mouse V1.

neuroscience↗

bioRxiv2022

Membrane potential dynamics of cerebellar nuclei neurons during eyeblink conditioning

Associative learning during delay eyeblink conditioning (EBC) depends on an intact cerebellum. However, the relative contribution of changes in the cerebellar nuclei to learning remains a subject of ongoing debate. In particular, little is known about the changes in synaptic inputs to cerebellar nuclei neurons that take place during EBC and how they shape the membrane potential of these neurons. Here, we probed the ability of these inputs to support associative learning in mice, and investigated structural and cell-physiological changes within the cerebellar nuclei during learning. We find that optogenetic stimulation of mossy fiber afferents to the anterior interposed nucleus (AIP) can substitute for a conditioned stimulus and is sufficient to elicit conditioned responses (CRs) that are adaptively well-timed. Further, EBC induces structural changes in mossy fiber and inhibitory inputs, but not of climbing fiber inputs, and it leads to changes in subthreshold processing of AIP neurons that correlate with conditioned eyelid movements. The changes in synaptic and spiking activity that precede the CRs allow for a decoder to distinguish trials with a CR. Our data reveal how structural and physiological modifications of synaptic inputs to cerebellar nuclei neurons can facilitate learning.

neuroscience↗

bioRxiv2019

Cerebellar plasticity and associative memories are controlled by perineuronal nets

Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN) but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity. When memories are fully acquired, PNNs are restored. Enzymatic digestion of PNNs in the DCN improves EBC learning, but intact PNNs are necessary for memory retention. At the structural level, PNN removal induces significant synaptic rearrangements in vivo, resulting in increased inhibition of DCN baseline activity in awake behaving mice. Together, these results demonstrate that PNNs are critical players in the regulation of cerebellar circuitry and function.

neuroscience↗

bioRxiv2018

Action perception recruits the cerebellum and is impaired in spinocerebellar ataxia patients

Our cerebellum has been proposed to generate prediction signals that may help us plan and execute our motor programs. However, to what extent our cerebellum is also actively involved in perceiving the action of others remains to be elucidated. Using fMRI, we show here that observing goal-directed hand actions of others bilaterally recruits cerebellar Lobules VI, VIIb and VIIIa. Moreover, whereas healthy subjects (n=31) were found to be able to discriminate subtle differences in the kinematics of observed limb movements of others, patients suffering from spinocerebellar ataxia type 6 (SCA6; n=21) were severely impaired in performing such tasks. Our data suggest that the human cerebellum is actively involved in perceiving the kinematics of the hand actions of others and that SCA6 patients deficits include a difficulty in perceiving the actions of other individuals. This finding alerts us to the fact that cerebellar disorders can alter social cognition. Given that impairments in social cognition have been reported to be one of the most debilitating consequences of neurological disorders, this finding may be relevant to improving the quality of life of patients and their families.

neuroscience↗