Multisensory task demands temporally extend the causal requirement for visual cortex in perception

Primary sensory areas constitute crucial nodes during perceptual decision making. However, it remains unclear to what extent they mainly constitute a feedforward processing step, or rather are continuously involved in a recurrent network together with higher-order areas. We found that the temporal window in which primary visual cortex is required for the detection of identical visual stimuli was extended when task demands were increased via an additional sensory modality that had to be monitored. Late-onset optogenetic inactivation preserved bottom-up, early-onset responses which faithfully encoded stimulus features, and was effective in impairing detection only if it preceded a late, report-related phase of the cortical response. Increasing task demands were marked by longer reaction times and the effect of late optogenetic inactivation scaled with reaction time. Thus, independently of visual stimulus complexity, multisensory task demands determine the temporal requirement for ongoing sensory-related activity in V1, which overlaps with report-related activity

Somatodendritic secretion in oxytocin neurons is upregulated during the female reproductive cycle

During the female reproductive cycle, hypothalamic oxytocin (OT) neurons undergo sharp changes in excitability. In lactating mammals, bursts of electrical activity of OT neurons result in the release of large amounts of OT in the bloodstream, which causes milk ejection. One hypothesis is that OT neurons regulate their own firing activity and that of nearby OT neurons by somatodendritic release of OT. In this study, we show that OT neuron activity strongly reduces inhibitory synaptic transmission to these neurons. This effect is blocked by antagonists of both adenosine and OT receptors and is mimicked by OT application. Inhibition of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex formation by tetanus toxin completely blocked the stimulation-induced reduction in inhibitory input, as did the calcium chelator BAPTA. During lactation, the readily releasable pool of secretory vesicles in OT cell bodies was doubled, and calcium currents were upregulated. This resulted in an increased inhibition of GABAergic synaptic transmission by somatodendritic release during lactation compared with the adult virgin stage. These results demonstrate that somatodendritic release is augmented during lactation, which is a novel form of plasticity to change the strength of synaptic transmission

Dendrites impact the encoding capabilities of the axon.

This study highlights a new and powerful direct impact of the dendritic tree (the input region of neurons) on the encoding capability of the axon (the output region). We show that the size of the dendritic arbors (its impedance load) strongly modulates the shape of the action potential (AP) onset at the axon initial segment; it is accelerated in neurons with larger dendritic surface area. AP onset rapidness is key in determining the capability of the axonal spikes to encode (phase lock to) rapid changes in synaptic inputs. Hence, our findings imply that neurons with larger dendritic arbors have improved encoding capabilities. This "dendritic size effect" was explored both analytically as well as numerically, in simplified and detailed models of 3D reconstructed layer 2/3 cortical pyramidal cells of rats and humans. The cutoff frequency of spikes phase locking to modulated inputs increased from 100 to 200 Hz in pyramidal cells of young rats to 400-600 Hz in human cells. In the latter case, phase locking reached close to 1 KHz in in vivo-like conditions. This work highlights new and functionally profound cross talk between the dendritic tree and the axon initial segment, providing new understanding of neurons as sophisticated nonlinear input/output devices. © 2014 the authors

Juxtasomal biocytin labeling to study the structure-function relationship of individual cortical neurons.

The cerebral cortex is characterized by multiple layers and many distinct cell-types that together as a network are responsible for many higher cognitive functions including decision making, sensory-guided behavior or memory. To understand how such intricate neuronal networks perform such tasks, a crucial step is to determine the function (or electrical activity) of individual cell types within the network, preferentially when the animal is performing a relevant cognitive task. Additionally, it is equally important to determine the anatomical structure of the network and the morphological architecture of the individual neurons to allow reverse engineering the cortical network. Technical breakthroughs available today allow recording cellular activity in awake, behaving animals with the valuable option of post hoc identifying the recorded neurons. Here, we demonstrate the juxtasomal biocytin labeling technique, which involves recording action potential spiking in the extracellular (or loose-patch) configuration using conventional patch pipettes The juxtasomal recording configuration is relatively stable and applicable across behavioral conditions, including anesthetized, sedated, awake head-fixed, and even in the freely moving animal. Thus, this method allows linking cell-type specific action potential spiking during animal behavior to reconstruction of the individual neurons and ultimately, the entire cortical microcircuit. In this video manuscript, we show how individual neurons in the juxtasomal configuration can be labeled with biocytin in the urethane-anaesthetized rat for post hoc identification and morphological reconstruction

Layer-specific modulation of the prefrontal cortex by nicotinic acetylcholine receptors

Acetylcholine signaling through nicotinic receptors (nAChRs) in the prefrontal cortex (PFC) is crucial for attention. Nicotinic AChRs are expressed on glutamatergic inputs to layer V (LV) cells and on LV interneurons and LVI pyramidal neurons. Whether PFC layers are activated by nAChRs to a similar extent or whether there is layer-specific activation is not known. Here, we investigate nAChR modulation of all PFC layers and find marked layer specificity for pyramidal neurons: LII/III pyramidal neurons and glutamatergic inputs to these cells do not contain nAChRs, LV and LVI pyramidal neurons are modulated by α7 and β2* nAChRs, respectively. Interneurons across layers contain mixed combinations of nAChRs. We then tested the hypothesis that nAChRs activate the PFC in a layer-specific manner using 2-photon population imaging. In all layers, nAChR-induced neuronal firing was dominated by β2* nAChRs. In LII/III, only interneurons were activated. In LV and LVI, both interneurons and pyramidal neurons were activated, the latter most strongly in LVI. Together, these results suggest that in the PFC nAChR activation results in inhibition of LII/III pyramidal neurons. In LV and LVI, nAChR-induced activation of inhibitory and excitatory neurons results in a net augmentation of output neuron activity. © 2012 The Author

Beyond Columnar Organization: Cell Type- and Target Layer-Specific Principles of Horizontal Axon Projection Patterns in Rat Vibrissal Cortex.

Vertical thalamocortical afferents give rise to the elementary functional units of sensory cortex, cortical columns. Principles that underlie communication between columns remain however unknown. Herewe unravel these by reconstructing in vivo-labeled neurons from all excitatory cell types in the vibrissal part of rat primary somatosensory cortex (vS1). Integrating the morphologies into an exact 3D model of vS1 revealed that the majority of intracortical (IC) axons project far beyond the borders of the principal column.We defined the corresponding innervation volume as the IC-unit. Deconstructing this structural cortical unit into its cell type-specific components,we found asymmetric projections that innervate columns of either the samewhisker rowor arc, and which subdivide vS1 into 2 orthogonal [supra-]granularand infragranular strata.We showthat such organization could be most effective for encoding multi whisker inputs. Communication between columns is thus organized by multiple highly specific horizontal projection patterns, rendering IC-units as the primary structural entities for processing complex sensory stimuli

Driver or coincidence detector: Modal switch of a corticothalamic giant synapse controlled by spontaneous activity and short-term depression

Giant synapses between layer 5B (L5B) neurons of somatosensory (barrel) cortex and neurons of the posteromedial nucleus (POm) of thalamus reside in a key position of the cortico-thalamo-cortical (CTC) loop, yet their synaptic properties and contribution to CTC information processing remain poorly understood. Fluorescence-guided local stimulation of terminals were combined with postsynaptic whole-cell recordings in thalamus to study synaptic transmission at an identified giant synapse. We found large EPSCs mediated by Ca2+-permeable AMPA and NMDA receptors. A single presynaptic electrical stimulus evoked a train of postsynaptic action potentials, indicating that a single L5B input can effectively drive the thalamic neuron. Repetitive stimulation caused strong short-term depression (STD) with fast recovery. To examine how these synaptic properties affect information transfer, spontaneous and evoked activity of L5B neurons was recorded in vivo and played back to giant terminals in vitro. We found that suprathreshold synaptic transmission was suppressed because of spontaneous activity causing strong STD of the L5B-POm giant synapse. Thalamic neurons only spiked after intervals of presynaptic silence or when costimulating two giant terminals. Therefore, STD caused by spontaneous activity of L5B neurons can switch the synapse from a "driver mode" to a "coincidence mode." Mechanisms decreasing spontaneous activity in L5B neurons and inputs synchronized by a sensory stimulus may thus gate the cortico-thalamo-cortical loop. Copyrigh