Biology subjects

Lohof, A. M.

Publications and source records attributed to Lohof, A. M..

5 recordsLinked to original sources

bioRxiv2026

Age-related cerebellar genetic, neuronal and functional impairments are reversed by specific magnetic stimulation protocols

Age-related cognitive decline reflects progressive atrophic changes that advance through broad neural networks. There is no effective treatment. However, brain ageing is not homogenous, so treating the earliest-affected circuits may be successful in reversing and/or preventing ongoing neuronal atrophy and therefore cognitive decline. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique that modulates cortical excitability, induces activity-dependent neuronal plasticity. Here we investigate short- and long-term effects of low intensity rTMS (LI-rTMS) on the cerebellum, which is adversely affected early during ageing. With age, cerebellar genes related to inflammation are strongly upregulated, whereas processes of synaptic-maintenance are reduced. Both abnormalities are rapidly corrected by LI-rTMS in a protocol-dependent manner. In parallel, LI-rTMS increases neuronal spine density and dendritic complexity, in association with improved spatial memory in both young adult and aged mice. These responses of the ageing cerebellum to low-intensity magnetic stimulation are extremely encouraging for treating age-related cognitive decline, but reinforce that appropriate stimulation parameters must be identified for effective treatment.

neuroscience↗

bioRxiv2025

Multivesicular release at a small central excitatory synaptic contact

We set out to study the properties of excitatory synaptic transmission at a central connection likely to consist of a single small synaptic contact. In the cerebellar cortex, molecular layer interneurones extend sparse thin dendrites in a parasagittal plane. The nonbranching parallel fibres traverse at right angles to the dendritic plane, forming en passant excitatory synapses. This arrangement makes it very likely that any synaptic connection between a parallel fibre and an interneurone will involve only a single contact. We obtained 20 paired recordings of synaptically connected granule cells and interneurones in cerebellar slices of immature rat, recorded at room temperature. Three of these pairs were successfully labelled using biocytin and a single point of contact between them was indentified. In 19/20 recordings, multiple release events corresponding to asynchronously released vesicles were frequently resolved following a single action potential. The frequency of these events could not be accounted for by spontaneous EPSCs, whose frequency was very low. We conclude that at this excitatory synaptic contact an action potential can release more than one vesicle.

neuroscience↗

bioRxiv2022

In vivo low-intensity magnetic pulses durably alter neocortical neuron excitability and spontaneous activity.

Magnetic brain stimulation is a promising treatment for neurological and psychiatric disorders. However, a better understanding of its effects at the individual neuron level is essential to improve its clinical application. We combined focal low-intensity repetitive transcranial magnetic stimulation (LI-rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neurons in vivo. Continuous 10 Hz LI-rTMS reliably evoked firing at [~]4-5 Hz during the stimulation period and induced durable attenuation of synaptic activity and spontaneous firing in cortical neurons, through membrane hyperpolarization and a reduced intrinsic excitability. However, inducing firing in individual neurons by repeated intracellular current injection did not reproduce LI-rTMS effects on neuronal properties. These data provide novel understanding of mechanisms underlying magnetic brain stimulation showing that, in addition to inducing biochemical plasticity, even weak magnetic fields can activate neurons and enduringly modulate their excitability.

neuroscience↗

bioRxiv2021

Pax3 induces neural circuit repair through a developmental program of directed axon outgrowth.

Repairing damaged or dysfunctional human brain circuits remains an ongoing challenge for biomedical science. While surviving neuronal networks can be reorganised after lesion, for example by neurotrophins, these new connections are disorganised and rarely produce clinical improvement. Here we investigate how to promote axonal growth while retaining correct cellular targeting. We show that, in response to brain-derived neurotrophic factor (BDNF) in target-tissue, potential reinnervating neurons upregulate Pax3. Pax3 in turn increases polysialic acid-neural cell adhesion molecule (PSA-NCAM) on their axon terminals, facilitating their outgrowth and pathfinding, and resulting in correctly-targeted neural circuit repair in the mature nervous system. This is a novel role for Pax3, which we confirmed by showing its expression in afferent neurons is essential for spontaneous and BDNF-induced reinnervation in the developing and mature brains, respectively. Together these results suggest that Pax3 contributes to a repair program, in which axon growth is promoted and direction signaling maintained. These data advance our understanding for accurately rebuilding neural circuits: restricting growth-promotion to potential afferent neurons, as opposed to stimulating the whole circuit, allows axon growth without impairing its guidance.

neuroscience↗

bioRxiv2018

Neural circuit repair by low-intensity magnetic stimulation requires cryptochrome

Magnetic brain stimulation is a promising treatment in neurology and psychiatry, but clinical outcomes are variable. Unfortunately, mechanisms underlying magnetic stimulation effects are ill-defined, which impedes the development of stimulation protocols appropriate for different neurological conditions. Here we show, in vivo and ex vivo, that repetitive transcranial magnetic stimulation at low-intensity (LI-rTMS) induces axon outgrowth and synaptogenesis to repair a neural circuit. This repair depends on stimulation pattern, with complex patterns being particularly effective, and its mechanism requires the presence of cryptochrome (Cry), a putative magneto-receptor. Effective LI-rTMS patterns altered expression of Cry target genes known to promote neuronal repair. Because LI-rTMS generates electric fields too weak to depolarise neurons, these findings indicate that the magnetic field itself induces the repair. Our data open a new framework for magnetic stimulation - cryptochrome-mediated molecular and structural neuroplasticity. This information suggests new routes to treatments specific for each neurological disease.

neuroscience↗