Although interactions between the thalamus and cortex are critical for cognitive function, the exact contribution of the thalamus to these interactions remains unclear. Recent studies have shown diverse connectivity patterns across the thalamus, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions is unknown. Here we show, by investigating the representation of two rules used to guide attention in the mouse prefrontal cortex (PFC), that the mediodorsal thalamus sustains these representations without relaying categorical information. Specifically, mediodorsal input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioural performance, whereas enhancing mediodorsal excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function, which is dissociable from categorical information relay, indicates that the thalamus has a much broader role in cognition than previously thought.

/pdf/thalamic-amplification-of-cortical-connectivity-sustains-21cxca18h1.pdf

Thalamic amplification of cortical connectivity sustains attentional control

Circuits in the cerebral cortex consist of thousands of neurons connected by millions of synapses. A precise understanding of these local networks requires relating circuit activity with the underlying network structure. For pyramidal cells in superficial mouse visual cortex (V1), a consensus is emerging that neurons with similar visual response properties excite each other, but the anatomical basis of this recurrent synaptic network is unknown. Here we combined physiological imaging and large-scale electron microscopy to study an excitatory network in V1. We found that layer 2/3 neurons organized into subnetworks defined by anatomical connectivity, with more connections within than between groups. More specifically, we found that pyramidal neurons with similar orientation selectivity preferentially formed synapses with each other, despite the fact that axons and dendrites of all orientation selectivities pass near (<5 μm) each other with roughly equal probability. Therefore, we predict that mechanisms of functionally specific connectivity take place at the length scale of spines. Neurons with similar orientation tuning formed larger synapses, potentially enhancing the net effect of synaptic specificity. With the ability to study thousands of connections in a single circuit, functional connectomics is proving a powerful method to uncover the organizational logic of cortical networks.

Anatomy and function of an excitatory network in the visual cortex

Predictive Processing: A Canonical Cortical Computation.

A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra" Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists' Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables

/pdf/diverse-coupling-of-neurons-to-populations-in-sensory-cortex-499uix3wef.pdf

Diverse coupling of neurons to populations in sensory cortex

INTRODUCTION Perceptual experiences in mammals may arise from patterns of neural circuit activity in cerebral cortex. For example, primary visual cortex (V1) is causally capable of initiating visual perception; in human neurosurgery patients, V1 electrical microstimulation has been reported to elicit basic visual percepts including spots of light, patterns, shapes, motions, and colors. Related phenomena have been studied in laboratory animals using similar electrical stimulation procedures, although detailed investigation has been difficult because studies of percept initiation in cortex have not involved groups of neurons individually selected for stimulation. Therefore, it is not clear how different percepts arise in cortex, nor why some stimuli fail to generate perceptual experiences. Answering these questions will require working with basic cellular elements within cortical circuit architecture during perception. RATIONALE To understand how circuits in V1 are specifically involved in visual perception, it is essential to probe, at the most basic cellular level, how behaviorally consequential percepts are initiated and maintained. In this study, we developed and implemented several key technological advances that together enable writing neural activity into dozens of single neurons in mouse V1 at physiological time scales. These methods also enabled us to simultaneously read out the impact of this stimulation on downstream network activity across hundreds of nearby neurons. Successful training of alert mice to discriminate the precisely defined circuit inputs enabled systematic investigation of basic cortical dynamics underlying perception. RESULTS We developed an experimental approach to drive large numbers of individually specified neurons, distributed across V1 volumes and targeted on the basis of natural response-selectivity properties observed during specific visual stimuli (movies of drifting horizontal or vertical gratings). To implement this approach, we built an optical read-write system capable of kilohertz speed, millimeter-scale lateral scope, and three-dimensional (3D) access across superficial to deep layers of cortex to tens or hundreds of individually specified neurons. This system was integrated with an unusual microbial opsin gene identified by crystal structure–based genome mining: ChRmine, named after the deep-red color carmine. This newly identified opsin confers properties crucial for cellular-resolution percept-initiation experiments: red-shifted light sensitivity, extremely large photocurrents alongside millisecond spike-timing fidelity, and compatibility with simultaneous two-photon Ca2+ imaging. Using ChRmine together with custom holographic devices to create arbitrarily specified light patterns, we were able to measure naturally occurring large-scale 3D ensemble activity patterns during visual experience and then replay these natural patterns at the level of many individually specified cells. We found that driving specific ensembles of cells on the basis of natural stimulus-selectivity resulted in recruitment of a broad network with dynamical patterns corresponding to those elicited by real visual stimuli and also gave rise to the correctly selective behaviors even in the absence of visual input. This approach allowed mapping of the cell numbers, layers, network dynamics, and adaptive events underlying generation of behaviorally potent percepts in neocortex, via precise control over naturally occurring, widely distributed, and finely resolved temporal parameters and cellular elements of the corresponding neural representations. CONCLUSION The cortical population dynamics that emerged after optogenetic stimulation both predicted the correctly elicited behavior and mimicked the natural neural representations of visual stimuli.

Cortical layer–specific critical dynamics triggering perception

The strength of synaptic connections fundamentally determines how neurons influence each other's firing. Excitatory connection amplitudes between pairs of cortical neurons vary over two orders of magnitude, comprising only very few strong connections among many weaker ones. Although this highly skewed distribution of connection strengths is observed in diverse cortical areas, its functional significance remains unknown: it is not clear how connection strength relates to neuronal response properties, nor how strong and weak inputs contribute to information processing in local microcircuits. Here we reveal that the strength of connections between layer 2/3 (L2/3) pyramidal neurons in mouse primary visual cortex (V1) obeys a simple rule--the few strong connections occur between neurons with most correlated responses, while only weak connections link neurons with uncorrelated responses. Moreover, we show that strong and reciprocal connections occur between cells with similar spatial receptive field structure. Although weak connections far outnumber strong connections, each neuron receives the majority of its local excitation from a small number of strong inputs provided by the few neurons with similar responses to visual features. By dominating recurrent excitation, these infrequent yet powerful inputs disproportionately contribute to feature preference and selectivity. Therefore, our results show that the apparently complex organization of excitatory connection strength reflects the similarity of neuronal responses, and suggest that rare, strong connections mediate stimulus-specific response amplification in cortical microcircuits.

http://mouse.vision/pdfs/Cossell_2015_Nat.pdf

Functional organization of excitatory synaptic strength in primary visual cortex

https://hearingbrain.org/docs/pecka_neuron_2014.pdf

Elie N. Sader

Papers

Functional organization of excitatory synaptic strength in primary visual cortex

Experience-dependent specialization of receptive field surround for selective coding of natural scenes.