Cortical microcircuit

UNLABELLED: Linking sensory-evoked traveling waves to underlying circuit patterns is critical to understanding the neural basis of sensory perception. To form this link, we performed simultaneous electrophysiology and two-photon calcium imaging through transparent NeuroGrids and mapped touch-evoked cortical traveling waves and their underlying microcircuit dynamics. In awake mice, both passive and active whisker touch elicited traveling waves within and across barrels, with a fast early component followed by a variable late wave that lasted hundreds of milliseconds post-stimulus...

The plasticity of inhibitory interneurons (INs) plays an important role in the organization and maintenance of cortical microcircuits. Given the many different IN types, there is an even greater diversity in synapse-type-specific plasticity learning rules at excitatory to excitatory (E→I), I→E, and I→I synapses. I→I synapses play a key disinhibitory role in cortical circuits. Because they typically target other INs, vasoactive intestinal peptide (VIP) INs are often featured in I→I→E disinhibition, which upregulates activity in nearby excitatory neurons...

Synchronization is a key feature of the brain dynamics and is necessary for information transmission across brain regions and in higher brain functions like cognition, learning and memory. Experimental findings demonstrated that in cortical microcircuits there are multiple synapses between pairs of connected neurons. Synchronization of neurons in the presence of multiple synaptic connections may be relevant for optimal learning and memory, however, its effect on the dynamics of the neurons is not adequately studied...

The 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, non-invasive physiological biomarker for schizophrenia and related neuropsychiatric disorders. The 40 Hz ASSR might be amplified by synaptic interactions in cortical circuits, which are, in turn, disturbed in neuropsychiatric disorders. Here, we tested whether the 40 Hz ASSR in human auditory cortex depends on two key synaptic components of neuronal interactions within cortical circuits: excitation via N-methyl-aspartate glutamate (NMDA) receptors and inhibition via gamma-amino-butyric acid (GABA) receptors...

The primary motor cortex (M1) integrates sensory and cognitive inputs to generate voluntary movement. Its functional impairments have been implicated in the pathophysiology of motor symptoms in Parkinson's disease (PD). Specifically, dopaminergic degeneration and basal ganglia dysfunction entrain M1 neurons into the abnormally synchronized bursting pattern of activity throughout the cortico-basal ganglia-thalamocortical network. However, how degeneration of the midbrain dopaminergic neurons affects the anatomy, microcircuit connectivity, and function of the M1 network remains poorly understood...

The computational capabilities of neuronal networks are fundamentally constrained by their specific connectivity. Previous studies of cortical connectivity have mostly been carried out in rodents; whether the principles established therein also apply to the evolutionarily expanded human cortex is unclear. We studied network properties within the human temporal cortex using samples obtained from brain surgery. We analyzed multineuron patch-clamp recordings in layer 2-3 pyramidal neurons and identified substantial differences compared with rodents...

Throughout life, neuronal networks in the mammalian neocortex maintain a balance of excitation and inhibition, which is essential for neuronal computation1,2 . Deviations from a balanced state have been linked to neurodevelopmental disorders, and severe disruptions result in epilepsy3-5 . To maintain balance, neuronal microcircuits composed of excitatory and inhibitory neurons sense alterations in neural activity and adjust neuronal connectivity and function. Here we identify a signalling pathway in the adult mouse neocortex that is activated in response to increased neuronal network activity...

Understanding medium spiny neuron (MSN) physiology is essential to understand motor impairments in Parkinson's disease (PD) given the architecture of the basal ganglia. Here, we developed a custom three-chambered microfluidic platform and established a cortico-striato-nigral microcircuit partially recapitulating the striatal presynaptic landscape in vitro using induced pluripotent stem cell (iPSC)-derived neurons. We found that, cortical glutamatergic projections facilitated MSN synaptic activity, and dopaminergic transmission enhanced maturation of MSNs in vitro...

The error-related negativity and an N2-component recorded over medial frontal cortex index core functions of cognitive control. While they are known to originate from agranular frontal areas, the underlying microcircuit mechanisms remain elusive. Most insights about microcircuit function have been derived from variations of the so-called canonical microcircuit model. These microcircuit architectures are based extensively on studies from granular sensory cortical areas in monkeys, cats, and rodents. However, evidence has shown striking cytoarchitectonic differences across species and differences in the functional relationships across cortical layers in agranular compared to granular sensory areas...

Cortical dynamics and computations are strongly influenced by diverse GABAergic interneurons, including those expressing parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP). Together with excitatory (E) neurons, they form a canonical microcircuit and exhibit counterintuitive nonlinear phenomena. One instance of such phenomena is response reversal, whereby SST neurons show opposite responses to top-down modulation via VIP depending on the presence of bottom-up sensory input, indicating that the network may function in different regimes under different stimulation conditions...

Inflammation, reduced gamma-aminobutyric acidergic (GABAergic) function and altered neuroplasticity are co-occurring pathophysiologies in major depressive disorder (MDD). However, the link between these biological changes remains unclear. We hypothesized that inflammation induces deficits in GABAergic interneuron markers and that this effect is mediated by brain-derived neurotrophic factor (BDNF). We report here that systemic inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS) (0.125, 0...

UNLABELLED: The canonical microcircuit (CMC) has been hypothesized to be the fundamental unit of information processing in cortex. Each CMC unit is thought to be an interconnected column of neurons with specific connections between excitatory and inhibitory neurons across layers. Recently, we identified a conserved spectrolaminar motif of oscillatory activity across the primate cortex that may be the physiological consequence of the CMC. The spectrolaminar motif consists of local field potential (LFP) gamma-band power (40-150 Hz) peaking in superficial layers 2 and 3 and alpha/beta-band power (8-30 Hz) peaking in deep layers 5 and 6...

The author provides 4 design principles of how to make cortical microcircuits into neuromorphic hardwares, shedding light for the next generation neuromorphic hardware design.

Nearly 25 years ago, Dr. Patricia Goldman-Rakic published her review paper, "The 'Psychic' Neuron of the Cerebral Cortex," outlining the circuit-level dynamics, neurotransmitter systems, and behavioral correlates of pyramidal neurons in the cerebral cortex, particularly as they relate to working memory. In the decades since the release of this paper, the existing literature and our understanding of the pyramidal neuron have increased tremendously, and research is still underway to better characterize the role of the pyramidal neuron in both healthy and psychiatric disease states...

Human and non-human primate data clearly implicate the dorsolateral prefrontal cortex (dlPFC) as critical for advanced cognitive functions 1,2 . It is thought that intracortical synaptic architectures within dlPFC are the integral neurobiological substrate that gives rise to these processes, including working memory, inferential reasoning, and decision-making 3-7 . In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the 'canonical' cortical microcircuit 3,8 ...

Here, we present a protocol for quantifying pyramidal neuron hyperexcitability in a mouse model of STXBP1 neurodevelopmental encephalopathy (Stxbp1hap ). We describe steps for preparing brain slices, positioning electrodes, and performing an excitability test to investigate microcircuit failures. This protocol is based on recording layer 2/3 cortical pyramidal neurons in response to stimulation of two independent sets of excitatory axons that recruit feedforward inhibition microcircuits. For complete details on the use and execution of this protocol, please refer to Dos Santos et al...

Under what conditions can prefrontal cortex direct the composition of brain states, to generate coherent streams of thoughts? Using a simplified Potts model of cortical dynamics, crudely differentiated into two halves, we show that once activity levels are regulated, so as to disambiguate a single temporal sequence, whether the contents of the sequence are mainly determined by the frontal or by the posterior half, or by neither, depends on statistical parameters that describe its microcircuits. The frontal cortex tends to lead if it has more local attractors, longer lasting and stronger ones, in order of increasing importance...

Reduced inhibition by somatostatin-expressing interneurons is associated with depression. Administration of positive allosteric modulators of α5 subunit-containing GABAA receptor (α5-PAM) that selectively target this lost inhibition exhibit antidepressant and pro-cognitive effects in rodent models of chronic stress. However, the functional effects of α5-PAM on the human brain in vivo are unknown, and currently cannot be assessed experimentally. We modeled the effects of α5-PAM on tonic inhibition as measured in human neurons, and tested in silico α5-PAM effects on detailed models of human cortical microcircuits in health and depression...

Human brain imaging research using functional MRI (fMRI) has uncovered flexible variations in the functional connectivity between brain regions. While some of this variability likely arises from the pattern of information flow through circuits, it may also be influenced by rapid changes in effective synaptic strength at the molecular level, a phenomenon called Dynamic Network Connectivity (DNC) discovered in non-human primate circuits. These neuromodulatory molecular mechanisms are found in layer III of the macaque dorsolateral prefrontal cortex (dlPFC), the site of the microcircuits shown by Goldman-Rakic to be critical for working memory...

Gephyrin is the main scaffolding protein at inhibitory postsynaptic sites, and its clusters are the signaling hubs where several molecular pathways converge. Post-translational modifications (PTMs) of gephyrin alter GABAA receptor clustering at the synapse, but it is unclear how this affects neuronal activity at the circuit level. We assessed the contribution of gephyrin PTMs to microcircuit activity in the mouse barrel cortex by slice electrophysiology and in vivo two-photon calcium imaging of layer 2/3 (L2/3) pyramidal cells during single-whisker stimulation...