The neocortex is organized into discrete layers of excitatory neurons: layer 4 receives the densest ‘bottom up’ projection carrying external sensory data, while layers 2/3 and 5 receive ‘top down’ inputs from higher cortical areas that may convey sensory expectations and behavioral goals. A subset of cortical somatostatin (SST) neurons gate top down input and control sensory computation by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5. However, it is unknown whether an analogous inhibitory mechanism separately and specifically controls activity in layer 4. We hypothesized that distinct SST circuits might exist to inhibit specific cortical layers. By enforcing layer-specific inhibition, distinct SST subnetworks could mediate pathway-specific gain control, such as regulating the balance between bottom up and top down input. Employing a combination of high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal distinct and complementary SST circuits that specifically and reciprocally interconnect with excitatory cells in either layer 4 or layers 2/3 and 5. Our data further define a transcriptionally distinct SST neuronal sub-class that powerfully gates bottom up sensory activity during active sensation by regulating layer 4 activity. This integrated paradigm further represents a potentially generalizable approach to identify and characterize neuronal cell types and reveal their in vivo function.

Abstract A key assumption in studies of cortical functions is that excitatory principal neurons, but not inhibitory cells express calcium/calmodulin-dependent protein kinase II subunit α (CaMKIIα) resulting in a widespread use of CaMKIIα promoter-driven protein expression for principal cell manipulation and monitoring their activities. Using neuroanatomical and electrophysiological methods we demonstrate that in addition to pyramidal neurons, multiple types of cortical GABAegic cells are targeted by adeno-associated viral vectors (AAV) driven by the CaMKIIα promoter in both male and female mice. We tested the AAV5 and AAV9 serotype of viruses with either Channelrhodopsin 2 (ChR2)-mCherry or Archaerhodopsin-T-green fluorescent protein (GFP) constructs, with different dilutions. We show that in all cases, the reporter proteins can visualize a large fraction of different interneuron types, including parvalbumin (PV), somatostatin (SST), neuronal nitric oxide synthase (nNOS), neuropeptide Y (NPY), and cholecystokinin (CCK)-containing GABAergic cells, which altogether cover around 60% of the whole inhibitory cell population in cortical structures. Importantly, the expression of the excitatory opsin Channelrhodopsin 2 in the interneurons effectively drive spiking of infected GABAergic cells even if the immunodetectability of reporter proteins is ambiguous. Thus, our results challenge the use of CaMKIIα promoter-driven protein expression as a selective tool in targeting cortical glutamatergic neurons using viral vectors.

regular waves with a frequency range of 6 to 9 Hz, and the main groups of hippocampal neurons (pyramidal cells and granule cells) show sparse population The hippocampus (pl.: hippocampi), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the subiculum are components of the hippocampal formation located in the limbic system. The hippocampus plays important roles in the consolidation of information from short-term memory to long-term memory, a The hippocampus has received renewed attention for its role in social memory. Epileptic human subjects with depth electrodes in the left posterior, left anterior or right anterior hippocampus demonstrate distinct, individual cell responses when presented with faces of presumably recognizable famous people. Associations among facial and vocal identity were similarly mapped to the hippocampus of rhesus monkeys. Single neurons in the CA1 and CA3 responded strongly to social stimulus recognition by MRI. The CA2 was not distinguished, and may likely comprise a proportion of the claimed CA1 cells in the study. The dorsal CA2 and ventral CA1 subregions of the hippocampus have been implicated in social memory processing. Genetic inactivation of CA2 pyramidal neurons leads to pronounced loss of social memory, while maintaining intact sociability in mice. Similarly, ventral CA1 pyramidal neurons have also been demonstrated as critical for social memory under optogenetic control in mice. The…

of dendrites, and they distinguish the pyramidal cells from spiny stellate cells in the cortices. Pyramidal cells are found in the prefrontal cortex, the An apical dendrite is a dendrite that emerges from the apex of a pyramidal cell. Apical dendrites are one of two primary categories of dendrites, and they distinguish the pyramidal cells from spiny stellate cells in the cortices. Pyramidal cells are found in the prefrontal cortex, the hippocampus, the entorhinal cortex, the olfactory cortex, and other areas. Dendrite arbors formed by apical dendr Seizures activate stress mechanisms including the excitatory neuropeptide corticotropin-releasing hormone (CRH) from hippocampal neurons. CRH has been shown to interfere with dendritic growth and differentiation. Mice lacking this receptor possess exuberant dendritic trees. However, pyramidal cells exposed to CRH during the first week of life had atrophied dendrites. These stress-related changes reduced synaptic plasticity and caused learning and memory deficits later in life. As antagonists for CRH exist, there exists a potential to reverse or prevent these effects through pharmacological means. Studies of recurrent febrile seizures have shown that seizures resulted in impaired learning and memory but also disrupted signaling that normally results in activation of cAMP response element binding factor (CREB), a transcription factor. For rats tested in the inhibitory avoidance learning paradigm, normally an activation of CREB occurs by phosphorylation at Ser133. This activation is impaired following recurrent febrile seizures. A seizure-induced modification of a signaling cascade upstream of CREB is suggested by this. Adult rats with infant febrile seizures were treated with Rolipram, a…