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1. Layer 5 of cortex innervates the thalamic reticular nucleus in mice

   https://doi.org/10.1073/pnas.2205209119  

   Carroll, Briana J.; Sampathkumar, Vandana; Kasthuri, Narayanan; Sherman, S. Murray (September 2022, Proceedings of the National Academy of Sciences)

   Neurons in the thalamic reticular nucleus (TRN) are a primary source of inhibition to the dorsal thalamus and, as they are innervated in part by the cortex, are a means of corticothalamic regulation. Previously, cortical inputs to the TRN were thought to originate solely from layer 6 (L6), but we recently reported the presence of putative synaptic terminals from layer 5 (L5) neurons in multiple cortical areas in the TRN [J. A. Prasad, B. J. Carroll, S. M. Sherman, J. Neurosci. 40, 5785–5796 (2020)]. Here, we demonstrate with electron microscopy that L5 terminals from multiple cortical regions make bona fide synapses in the TRN. We further use light microscopy to localize these synapses relative to recently described TRN subdivisions and show that L5 terminals target the edges of the somatosensory TRN, where neurons reciprocally connect to higher-order thalamus, and that L5 terminals are scarce in the core of the TRN, where neurons reciprocally connect to first-order thalamus. In contrast, L6 terminals densely innervate both edge and core subregions and are smaller than those from L5. These data suggest that a sparse but potent input from L5 neurons of multiple cortical regions to the TRN may yield transreticular inhibition targeted to higher-order thalamus. 

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2. Complementary networks of cortical somatostatin interneurons enforce layer specific control

   https://doi.org/10.7554/eLife.43696  

   Naka, Alexander; Veit, Julia; Shababo, Ben; Chance, Rebecca K; Risso, Davide; Stafford, David; Snyder, Benjamin; Egladyous, Andrew; Chu, Desiree; Sridharan, Savitha; et al (March 2019, eLife)

   The neocortex is functionally organized into layers. Layer four receives the densest bottom up sensory inputs, while layers 2/3 and 5 receive top down inputs that may convey predictive information. A subset of cortical somatostatin (SST) neurons, the Martinotti cells, gate top down input by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5, but it is unknown whether an analogous inhibitory mechanism controls activity in layer 4. Using high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal complementary circuits in the mouse barrel cortex involving genetically distinct SST subtypes that specifically and reciprocally interconnect with excitatory cells in different layers: Martinotti cells connect with layers 2/3 and 5, whereas non-Martinotti cells connect with layer 4. By enforcing layer-specific inhibition, these parallel SST subnetworks could independently regulate the balance between bottom up and top down input. 

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3. Optogenetic stimulation shifts the excitability of cerebral cortex from type I to type II: oscillation onset and wave propagation

   Heitmann, S.; Rule, M.; Truccolo, W.; Ermentrout, B. (January 2017, PLOS computational biology)

   Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40–80 Hz) oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude—the hallmark of a type II excitable medium—yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields. 

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4. Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive interneurons

   https://doi.org/10.1016/j.celrep.2021.109972  

   Melander, Joshua B; Nayebi, Aran; Jongbloets, Bart C; Fortin, Dale A; Qin, Maozhen; Ganguli, Surya; Mao, Tianyi; Zhong, Haining (November 2021, Cell Reports)

   Cortical function relies on the balanced activation of excitatory and inhibitory neurons. However, little is known about the organization and dynamics of shaft excitatory synapses onto cortical inhibitory interneu- rons. Here, we use the excitatory postsynaptic marker PSD-95, fluorescently labeled at endogenous levels, as a proxy for excitatory synapses onto layer 2/3 pyramidal neurons and parvalbumin-positive (PV+) interneu- rons in the barrel cortex of adult mice. Longitudinal in vivo imaging under baseline conditions reveals that, although synaptic weights in both neuronal types are log-normally distributed, synapses onto PV+ neurons are less heterogeneous and more stable. Markov model analyses suggest that the synaptic weight distribu- tion is set intrinsically by ongoing cell-type-specific dynamics, and substantial changes are due to accumu- lated gradual changes. Synaptic weight dynamics are multiplicative, i.e., changes scale with weights, although PV+ synapses also exhibit an additive component. These results reveal that cell-type-specific pro- cesses govern cortical synaptic strengths and dynamics. 

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5. Theta activity paradoxically boosts gamma and ripple frequency sensitivity in prefrontal interneurons

   https://doi.org/10.1073/pnas.2114549118  

   Merino, Ricardo Martins; Leon-Pinzon, Carolina; Stühmer, Walter; Möck, Martin; Staiger, Jochen F.; Wolf, Fred; Neef, Andreas (December 2021, Proceedings of the National Academy of Sciences)

   Fast oscillations in cortical circuits critically depend on GABAergic interneurons. Which interneuron types and populations can drive different cortical rhythms, however, remains unresolved and may depend on brain state. Here, we measured the sensitivity of different GABAergic interneurons in prefrontal cortex under conditions mimicking distinct brain states. While fast-spiking neurons always exhibited a wide bandwidth of around 400 Hz, the response properties of spike-frequency adapting interneurons switched with the background input’s statistics. Slowly fluctuating background activity, as typical for sleep or quiet wakefulness, dramatically boosted the neurons’ sensitivity to gamma and ripple frequencies. We developed a time-resolved dynamic gain analysis and revealed rapid sensitivity modulations that enable neurons to periodically boost gamma oscillations and ripples during specific phases of ongoing low-frequency oscillations. This mechanism predicts these prefrontal interneurons to be exquisitely sensitive to high-frequency ripples, especially during brain states characterized by slow rhythms, and to contribute substantially to theta-gamma cross-frequency coupling. 

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