Review article: Translating STRIDE-II into clinical reality - Opportunities and challenges.

BACKGROUND: With the introduction of novel therapies for inflammatory bowel diseases (IBD), 'treat-to-target' strategies are increasingly discussed to improve short- and long-term outcomes in patients with IBD. AIM: To discuss opportunities and challenges of a treat-to-target approach in light of the current 'Selecting Therapeutic Targets in Inflammatory Bowel Disease' (STRIDE-II) consensus METHODS: The 2021 update of STRIDE-II encompasses 13 evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. We highlight the potential implications and limitations of these recommendations for clinical practice. RESULTS: STRIDE-II provides valuable guidance for personalised IBD management. It reflects scientific progress as well as increased evidence of improved outcomes when more ambitious treatment goals such as mucosal healing are achieved. CONCLUSIONS: Prospective studies, objective criteria for risk stratification, and better predictors of therapeutic response are needed to potentially render 'treating to target' more effective in the future.

Simultaneous patch-clamping and calcium imaging in developing dendrites.

Calcium imaging has been used extensively to explore the role of action potential (AP) firing in the development of neuronal structure and synaptic function because increases in intracellular calcium ([Ca(2+)]i) reliably and, within a certain range, linearly reflect neuronal spiking activity. Patterns of APs in individual cells can be deduced from calcium recordings, which have typically been performed at the level of cell bodies. However, neurons are particularly susceptible to phototoxicity when they are illuminated at the soma. Furthermore, for some imaging experiments (e.g., those that address the interactions between dendrites and axons during synapse formation), the cell body of a given neuron may simply not be in the field of view. In these situations, it would be helpful to determine the spiking patterns of a neuron from the calcium activity in its subcellular compartments such as stretches of dendrites or axons. Here, we describe an approach for determining the relationship between AP firing and dendritic calcium transients by simultaneously imaging calcium transients in small dendritic stretches of hippocampal pyramidal neurons in slice cultures from neonatal rats and recording spiking activity with whole-cell patch-clamp recordings in these neurons. These experiments allow us to correlate the electrophysiological spiking pattern with the accompanying changes in the calcium concentration in individual dendritic segments.

Activity-dependent clustering of functional synaptic inputs on developing hippocampal dendrites.

During brain development, before sensory systems become functional, neuronal networks spontaneously generate repetitive bursts of neuronal activity, which are typically synchronized across many neurons. Such activity patterns have been described on the level of networks and cells, but the fine-structure of inputs received by an individual neuron during spontaneous network activity has not been studied. Here, we used calcium imaging to record activity at many synapses of hippocampal pyramidal neurons simultaneously to establish the activity patterns in the majority of synapses of an entire cell. Analysis of the spatiotemporal patterns of synaptic activity revealed a fine-scale connectivity rule: neighboring synapses (<16 µm intersynapse distance) are more likely to be coactive than synapses that are farther away from each other. Blocking spiking activity or NMDA receptor activation revealed that the clustering of synaptic inputs required neuronal activity, demonstrating a role of developmentally expressed spontaneous activity for connecting neurons with subcellular precision.