Jeffery S. Isaacson

Bio: Jeffery S. Isaacson is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Neural Inhibition. The author has an hindex of 1, co-authored 1 publications receiving 1214 citations.

Inhibition of Inhibition in Visual Cortex: The Logic of Connections Between Molecularly Distinct Interneurons

Abstract: Cortical inhibitory neurons contact each other to form a network of inhibitory synaptic connections. Our knowledge of the connectivity pattern underlying this inhibitory network is, however, still incomplete. Here we describe a simple and complementary interaction scheme between three large, molecularly distinct interneuron populations in mouse visual cortex: parvalbumin-expressing interneurons strongly inhibit one another but provide little inhibition to other populations. In contrast, somatostatin-expressing interneurons avoid inhibiting one another yet strongly inhibit all other populations. Finally, vasoactive intestinal peptide-expressing interneurons preferentially inhibit somatostatin-expressing interneurons. This scheme occurs in supragranular and infragranular layers, suggesting that inhibitory networks operate similarly at the input and output of the visual cortex. Thus, as the specificity of connections between excitatory neurons forms the basis for the cortical canonical circuit, the scheme described here outlines a standard connectivity pattern among cortical inhibitory neurons.

Cortical interneurons that specialize in disinhibitory control

Abstract: In the mammalian cerebral cortex the diversity of interneuronal subtypes underlies a division of labour subserving distinct modes of inhibitory control. A unique mode of inhibitory control may be provided by inhibitory neurons that specifically suppress the firing of other inhibitory neurons. Such disinhibition could lead to the selective amplification of local processing and serve the important computational functions of gating and gain modulation. Although several interneuron populations are known to target other interneurons to varying degrees, little is known about interneurons specializing in disinhibition and their in vivo function. Here we show that a class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single-cell recordings, we examined the functional role of VIP interneurons in awake mice, and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. We identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells, respectively. During the performance of an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in auditory cortex, and in turn VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell type and microcircuit underlying disinhibitory control in cortex and demonstrate that it is activated under specific behavioural conditions.

Equalizing excitation–inhibition ratios across visual cortical neurons

Abstract: Different amounts of excitation received by different pyramidal cells of primary visual cortex are matched by proportional amounts of inhibition. The balance between synaptic excitation and inhibition in the mammalian sensory cortex — known as the E/I ratio — is an important influence on both sensory processing and cognitive function. The mechanisms that establish and maintain the E/I ratio are still poorly understood. It is not clear whether each cortical neuron has the ability of individually regulating its own E/I ratio or if the E/I ratio is equalized across the pyramidal cell population. In a study of mouse primary visual cortex, Massimo Scanziani and colleagues show that E/I ratios are remarkably similar across different pyramidal cells despite large variations in the amplitudes of synaptic excitation and inhibition. This is achieved through matched inhibition mediated by parvalbumin-expressing but not by somatostatin-expressing interneurons. The relationship between synaptic excitation and inhibition (E/I ratio), two opposing forces in the mammalian cerebral cortex, affects many cortical functions such as feature selectivity and gain1,2. Individual pyramidal cells show stable E/I ratios in time despite fluctuating cortical activity levels. This is because when excitation increases, inhibition increases proportionally through the increased recruitment of inhibitory neurons, a phenomenon referred to as excitation–inhibition balance3,4,5,6,7,8,9. However, little is known about the distribution of E/I ratios across pyramidal cells. Through their highly divergent axons, inhibitory neurons indiscriminately contact most neighbouring pyramidal cells10,11. Is inhibition homogeneously distributed12 or is it individually matched to the different amounts of excitation received by distinct pyramidal cells? Here we discover that pyramidal cells in layer 2/3 of mouse primary visual cortex each receive inhibition in a similar proportion to their excitation. As a consequence, E/I ratios are equalized across pyramidal cells. This matched inhibition is mediated by parvalbumin-expressing but not somatostatin-expressing inhibitory cells and results from the independent adjustment of synapses originating from individual parvalbumin-expressing cells targeting different pyramidal cells. Furthermore, this match is activity-dependent as it is disrupted by perturbing pyramidal cell activity. Thus, the equalization of E/I ratios across pyramidal cells reveals an unexpected degree of order in the spatial distribution of synaptic strengths and indicates that the relationship between the cortex’s two opposing forces is stabilized not only in time but also in space.

Expectation in perceptual decision making: neural and computational mechanisms

Abstract: Sensory signals are highly structured in both space and time. These structural regularities in visual information allow expectations to form about future stimulation, thereby facilitating decisions about visual features and objects. Here, we discuss how expectation modulates neural signals and behaviour in humans and other primates. We consider how expectations bias visual activity before a stimulus occurs, and how neural signals elicited by expected and unexpected stimuli differ. We discuss how expectations may influence decision signals at the computational level. Finally, we consider the relationship between visual expectation and related concepts, such as attention and adaptation.