Layer 1 NDNF interneurons are specialized top-down master regulators of cortical circuits.

Diverse types of inhibitory interneurons (INs) impart computational power and flexibility to neocortical circuits. Whereas markers for different IN types in cortical layers 2-6 (L2-L6) have been instrumental for generating a wealth of functional insights, only the recent identification of a selective marker (neuron-derived neurotrophic factor [NDNF]) has opened comparable opportunities for INs in L1 (L1INs). However, at present we know very little about the connectivity of NDNF L1INs with other IN types, their input-output conversion, and the existence of potential NDNF L1IN subtypes. Here, we report pervasive inhibition of L2/3 INs (including parvalbumin INs and vasoactive intestinal peptide INs) by NDNF L1INs. Intersectional genetics revealed similar physiology and connectivity in the NDNF L1IN subpopulation co-expressing neuropeptide Y. Finally, NDNF L1INs prominently and selectively engage in persistent firing, a physiological hallmark disconnecting their output from the current input. Collectively, our work therefore identifies NDNF L1INs as specialized master regulators of superficial neocortex according to their pervasive top-down afferents.

Preselector.uni-jena.de: optimize your cloning-a resource for identifying restriction enzymes for preselection reactions.

Preselection digests are a common strategy to reduce the background in the ligation step of molecular cloning. However, choosing fitting restriction enzymes by hand is not trivial and may lead to errors, potentially costing a lot of time and work. We therefore created preselector.uni-jena.de (https://preselector.uni-jena.de/), a free online tool to find such restriction enzymes. The tool uses regular expressions to find recognition sites of restriction enzymes in the DNA sequences provided by the user. This new tool compares the sets of restriction sites and reports the enzymes that cut one sequence but not the other sequences to the user. These enzymes are then the ones suitable for a preselection digest. Thus, preselector.uni-jena.de is a fast, reliable, and free-to-use tool to help researchers designing preselection digestion strategies for their cloning.

Inhibitory plasticity in layer 1 - dynamic gatekeeper of neocortical associations.

Neocortical layer 1 is a major site of convergence for a variety of brain wide afferents carrying experience-dependent top-down information, which are integrated and processed in the apical tuft dendrites of pyramidal cells. Two types of local inhibitory interneurons, Martinotti cells and layer 1 interneurons, dominantly shape dendritic integration, and work from recent years has significantly advanced our understanding of the role of these interneurons in circuit plasticity and learning. Both cell types instruct plasticity in local pyramidal cells, and are themselves subject to robust plastic changes. Despite these similarities, the emerging hypothesis is that they fulfill different, and potentially opposite roles, as they receive different inputs, employ distinct inhibitory dynamics and are implicated in different behavioral contexts.

A Critical Role for Neocortical Processing of Threat Memory.

Memory of cues associated with threat is critical for survival and a leading model for elucidating how sensory information is linked to adaptive behavior by learning. Although the brain-wide circuits mediating auditory threat memory have been intensely investigated, it remains unclear whether the auditory cortex is critically involved. Here we use optogenetic activity manipulations in defined cortical areas and output pathways, viral tracing, pathway-specific in vivo 2-photon calcium imaging, and computational analyses of population plasticity to reveal that the auditory cortex is selectively required for conditioning to complex stimuli, whereas the adjacent temporal association cortex controls all forms of auditory threat memory. More temporal areas have a stronger effect on memory and more neurons projecting to the lateral amygdala, which control memory to complex stimuli through a balanced form of population plasticity that selectively supports discrimination of significant sensory stimuli. Thus, neocortical processing plays a critical role in cued threat memory.