Structure and function of neocortical layer 6b

Cortical layer 6b is considered by many to be a remnant of the subplate that forms during early stages of neocortical development, but its role in the adult is not well understood. Its neuronal complement has only recently become the subject of systematic studies, and its axonal projections and synaptic input structures have remained largely unexplored despite decades of research into neocortical function. In recent years, however, layer 6b (L6b) has attracted increasing attention and its functional role is beginning to be elucidated. In this review, I will attempt to provide an overview of what is currently known about the excitatory and inhibitory neurons in this layer, their pre- and postsynaptic connectivity, and their functional implications. Similarities and differences between different cortical areas will be highlighted. Finally, layer 6b neurons are highly responsive to several neuropeptides such as orexin/hypocretin, neurotensin and cholecystokinin, in some cases exclusively. They are also strongly controlled by neurotransmitters such as acetylcholine and norepinephrine. The interaction of these neuromodulators with L6b microcircuitry and its functional consequences will also be discussed

Shared and divergent principles of synaptic transmission between cortical excitatory neurons in rodent and human brain

Information transfer between principal neurons in neocortex occurs through (glutamatergic) synaptic transmission. In this focussed review, we provide a detailed overview on the strength of synaptic neurotransmission between pairs of excitatory neurons in human and laboratory animals with a specific focus on data obtained using patch clamp electrophysiology. We reach two major conclusions: (1) the synaptic strength, measured as unitary excitatory postsynaptic potential (or uEPSP), is remarkably consistent across species, cortical regions, layers and/or cell-types (median 0.5 mV, interquartile range 0.4–1.0 mV) with most variability associated with the cell-type specific connection studied (min 0.1–max 1.4 mV), (2) synaptic function cannot be generalized across human and rodent, which we exemplify by discussing the differences in anatomical and functional properties of pyramidal-to-pyramidal connections within human and rodent cortical layers 2 and 3. With only a handful of studies available on synaptic transmission in human, it is obvious that much remains unknown to date. Uncovering the shared and divergent principles of synaptic transmission across species however, will almost certainly be a pivotal step toward understanding human cognitive ability and brain function in health and disease

Structural determinants underlying the high efficacy of synaptic transmission and plasticity at synaptic boutons in layer 4 of the adult rat 'barrel cortex'

Excitatory layer 4 (L4) neurons in the ‘barrel field’ of the rat somatosensory cortex represent an important component in thalamocortical information processing. However, no detailed information exists concerning the quantitative geometry of synaptic boutons terminating on these neurons. Thus, L4 synaptic boutons were investigated using serial ultrathin sections and subsequent quantitative 3D reconstructions. In particular, parameters representing structural correlates of synaptic transmission and plasticity such as the number, size and distribution of pre- and postsynaptic densities forming the active zone (AZ) and of the three functionally defined pools of synaptic vesicles were analyzed. L4 synaptic boutons varied substantially in shape and size; the majority had a single, but large AZ with opposing pre- and postsynaptic densities that matched perfectly in size and position. More than a third of the examined boutons showed perforations of the postsynaptic density. Synaptic boutons contained on average a total pool of 561 ± 108 vesicles, with ~5 % constituting the putative readily releasable, ~23 % the recycling, and the remainder the reserve pool. These pools are comparably larger than other characterized central synapses. Synaptic complexes were surrounded by a dense network of fine astrocytic processes that reached as far as the synaptic cleft, thus regulating the temporal and spatial glutamate concentration, and thereby shaping the unitary EPSP amplitude. In summary, the geometry and size of AZs, the comparably large readily releasable and recycling pools, together with the tight astrocytic ensheathment, may explain and contribute to the high release probability, efficacy and modulation of synaptic transmission at excitatory L4 synaptic boutons. Moreover, the structural variability as indicated by the geometry of L4 synaptic boutons, the presence of mitochondria and the size and shape of the AZs strongly suggest that synaptic reliability, strength and plasticity is governed and modulated individually at excitatory L4 synaptic boutons

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus

Local circuits targeting parvalbumin-containing interneurons in layer IV of rat barrel cortex

Interactions between inhibitory interneurons and excitatory spiny neurons and also other inhibitory cells represent fundamental network properties which cause the so-called thalamo-cortical response transformation and account for the well-known receptive field differences of cortical layer IV versus thalamic neurons. We investigated the currently largely unknown morphological basis of these interactions utilizing acute slice preparations of barrel cortex in P19-21 rats. Layer IV spiny (spiny stellate, star pyramidal and pyramidal) neurons or inhibitory (basket and bitufted) interneurons were electrophysiologically characterized and intracellularly biocytin-labeled. In the same slice, we stained parvalbumin-immunoreactive (PV-ir) interneurons as putative target cells after which the tissue was subjected to confocal image acquisition. Parallel experiments confirmed the existence of synaptic contacts in these types of connection by correlated light and electron microscopy. The axons of the filled neurons differentially targeted barrel PV-ir interneurons: (1) The relative number of all contacted PV-ir cells within the axonal sphere was 5–17% for spiny (n = 10), 32 and 58% for basket (n = 2) and 12 and 13% for bitufted (n = 2) cells. (2) The preferential subcellular site which was contacted on PV-ir target cells was somatic for four and dendritic for five spiny cells; for basket cells, there was a somatic and for bitufted cells a dendritic preference in each examined case. (3) The highest number of contacts on a single PV-ir cell was 9 (4 somatic and 5 dendritic) for spiny neurons, 15 (10 somatic and 5 dendritic) for basket cells and 4 (1 somatic and 3 dendritic) for bitufted cells. These patterns suggest a cell type-dependent communication within layer IV microcircuits in which PV-ir interneurons provide not only feed-forward but also feedback inhibition thus triggering the thalamo-cortical response transformation

Layer- and Cell Type-Specific Modulation of Excitatory Neuronal Activity in the Neocortex

From an anatomical point of view the neocortex is subdivided into up to six layers depending on the cortical area. This subdivision has been described already by Meynert and Brodmann in the late 19/early 20. century and is mainly based on cytoarchitectonic features such as the size and location of the pyramidal cell bodies. Hence, cortical lamination is originally an anatomical concept based on the distribution of excitatory neuron. However, it has become apparent in recent years that apart from the layer-specific differences in morphological features, many functional properties of neurons are also dependent on cortical layer or cell type. Such functional differences include changes in neuronal excitability and synaptic activity by neuromodulatory transmitters. Many of these neuromodulators are released from axonal afferents from subcortical brain regions while others are released intrinsically. In this review we aim to describe layer- and cell-type specific differences in the effects of neuromodulator receptors in excitatory neurons in layers 2–6 of different cortical areas. We will focus on the neuromodulator systems using adenosine, acetylcholine, dopamine, and orexin/hypocretin as examples because these neuromodulator systems show important differences in receptor type and distribution, mode of release and functional mechanisms and effects. We try to summarize how layer- and cell type-specific neuromodulation may affect synaptic signaling in cortical microcircuits

Excitatory neuronal connectivity in the barrel cortex

Neocortical areas are believed to be organized into vertical modules, the cortical columns, and the horizontal layers 1–6. In the somatosensory barrel cortex these columns are defined by the readily discernible barrel structure in layer 4. Information processing in the neocortex occurs along vertical and horizontal axes, thereby linking individual barrel-related columns via axons running through the different cortical layers of the barrel cortex. Long-range signaling occurs within the neocortical layers but also through axons projecting through the white matter to other neocortical areas and subcortical brain regions. Because of the ease of identification of barrel-related columns, the rodent barrel cortex has become a prototypical system to study the interactions between different neuronal connections within a sensory cortical area and between this area and other cortical as well subcortical regions. Such interactions will be discussed specifically for the feed-forward and feedback loops between the somatosensory and the somatomotor cortices as well as the different thalamic nuclei. In addition, recent advances concerning the morphological characteristics of excitatory neurons and their impact on the synaptic connectivity patterns and signaling properties of neuronal microcircuits in the whisker-related somatosensory cortex will be reviewed. In this context, their relationship between the structural properties of barrel-related columns and their function as a module in vertical synaptic signaling in the whisker-related cortical areas will be discussed

A barrel-related interneuron in layer 4 of rat somatosensory cortex with a high intra-barrel connectivity

Synaptic connections between identified fast-spiking (FS), parvalbu-min (PV)-positive interneurons, and excitatory spiny neurons in layer 4 (L4) of the barrel cortex were investigated using patch-clamp re-cordings and simultaneous biocytin fillings. Three distinct clusters of FS L4 interneurons were identified based on their axonal morphology relative to the barrel column suggesting that these neurons do not constitute a homogeneous interneuron population. One L4 FS inter-neuron type had an axonal domain strictly confined to a L4 barrel and was therefore named “barrel-confined inhibitory interneuron ” (BIn). BIns established reliable inhibitory synaptic connections with L4 spiny neurons at a high connectivity rate of 67%, of which 69 % were reci-procal. Unitary IPSPs at these connections had a mean amplitude of 0.9 ± 0.8 mV with little amplitude variation and weak short-term sy-naptic depression. We found on average 3.7 ± 1.3 putative inhibitory synaptic contacts that were not restricted to perisomatic areas. I