Functional constraints in the evolution of brain circuits

Regardless of major anatomical and neurodevelopmental differences, the vertebrate isocortex shows a remarkably well-conserved organization. In the isocortex, reciprocal connections between excitatory and inhibitory neurons are distributed across multiple layers, encompassing modular, dynamical and recurrent functional networks during information processing. These dynamical brain networks are often organized in neuronal assemblies interacting through rhythmic phase relationships. Accordingly, these oscillatory interactions are observed across multiple brain scale levels, and they are associated with several sensory, motor, and cognitive processes. Most notably, oscillatory interactions are also found in the complete spectrum of vertebrates. Yet, it is unknown why this functional organization is so well conserved in evolution. In this perspective, we propose some ideas about how functional requirements of the isocortex can account for the evolutionary stability observed in microcircuits across vertebrates. We argue that isocortex architectures represent canonical microcircuits resulting from: (i) the early selection of neuronal architectures based on the oscillatory excitatory-inhibitory balance, which lead to the implementation of compartmentalized oscillations and (ii) the subsequent emergence of inferential coding strategies (predictive coding), which are able to expand computational capacities. We also argue that these functional constraints may be the result of several advantages that oscillatory activity contributes to brain network processes, such as information transmission and code reliability. In this manner, similarities in mesoscale brain circuitry and input-output organization between different vertebrate groups may reflect evolutionary constraints imposed by these functional requirements, which may or may not be traceable to a common ancestor

The thalamocortical symphony:How thalamus and cortex play together in schizophrenia and plasticity

The work presented in this thesis aimed at investigating the function and mechanism of corticothalamic-thalamocortical network in schizophrenia and experience-dependent plasticity, further discussed their possible connection.In Chapter 2, we examined the effects of low-dose ketamine on the corticothalamic circuit (CTC) system. Our findings reveal that ketamine induces abnormal spindle activity and gamma oscillations in the CTC system. Notably, ketamine also leads to a transition in thalamic neurons from burst-firing to tonic action potential mode, which may underlie deficits in spindle oscillations. Chapter 3 addresses sensory perception deficits in schizophrenia, emphasizing disruptions in beta and gamma frequency oscillations due to signal-to-noise ratio imbalances. Chapter 4 explores experience-dependent plasticity, highlighting the role of thalamic synaptic inhibition in ocular dominance plasticity and the influence of cortical feedback. Chapter 5 investigates the involvement of endocannabinoids, particularly CB1 receptors, in inhibitory synaptic maturation and ocular dominance plasticity within the primary visual cortex.The general discussion raises the possibility of a link between neural plasticity and schizophrenia, particularly during the transformative phase of adolescence when the brain undergoes significant changes. An abnormal balance between inhibition and excitation, influenced by GABAergic maturation deficits, connectivity disruptions, and altered perceptual information transfer, may contribute to the development of schizophrenia.This thesis offers valuable insights into the intricate mechanisms underlying schizophrenia, with a particular focus on the CTC circuit, NMDA receptors, and endocannabinoids in the context of neuronal plasticity and cognitive function

The thalamocortical symphony:How thalamus and cortex play together in schizophrenia and plasticity

The work presented in this thesis aimed at investigating the function and mechanism of corticothalamic-thalamocortical network in schizophrenia and experience-dependent plasticity, further discussed their possible connection.In Chapter 2, we examined the effects of low-dose ketamine on the corticothalamic circuit (CTC) system. Our findings reveal that ketamine induces abnormal spindle activity and gamma oscillations in the CTC system. Notably, ketamine also leads to a transition in thalamic neurons from burst-firing to tonic action potential mode, which may underlie deficits in spindle oscillations. Chapter 3 addresses sensory perception deficits in schizophrenia, emphasizing disruptions in beta and gamma frequency oscillations due to signal-to-noise ratio imbalances. Chapter 4 explores experience-dependent plasticity, highlighting the role of thalamic synaptic inhibition in ocular dominance plasticity and the influence of cortical feedback. Chapter 5 investigates the involvement of endocannabinoids, particularly CB1 receptors, in inhibitory synaptic maturation and ocular dominance plasticity within the primary visual cortex.The general discussion raises the possibility of a link between neural plasticity and schizophrenia, particularly during the transformative phase of adolescence when the brain undergoes significant changes. An abnormal balance between inhibition and excitation, influenced by GABAergic maturation deficits, connectivity disruptions, and altered perceptual information transfer, may contribute to the development of schizophrenia.This thesis offers valuable insights into the intricate mechanisms underlying schizophrenia, with a particular focus on the CTC circuit, NMDA receptors, and endocannabinoids in the context of neuronal plasticity and cognitive function

Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate realistic models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems

Towards building a more complex view of the lateral geniculate nucleus: Recent advances in understanding its role

The lateral geniculate nucleus (LGN) has often been treated in the past as a linear filter that adds little to retinal processing of visual inputs. Here we review anatomical, neurophysiological, brain imaging, and modeling studies that have in recent years built up a much more complex view of LGN . These include effects related to nonlinear dendritic processing, cortical feedback, synchrony and oscillations across LGN populations, as well as involvement of LGN in higher level cognitive processing. Although recent studies have provided valuable insights into early visual processing including the role of LGN, a unified model of LGN responses to real-world objects has not yet been developed. In the light of recent data, we suggest that the role of LGN deserves more careful consideration in developing models of high-level visual processing

Communication between Brain Areas Based on Nested Oscillations

Contains fulltext : 168625.pdf (publisher's version ) (Open Access)14 p

The Mechanisms And Roles Of Feedback Loops For Visual Processing

Signal flow in the brain is not unidirectional; feedback represents a key element in neural signal processing. To address the question on how do neural feedback loops work in terms of synapses, microcircuitry, and systems dynamics, we developed a chick midbrain slice preparation to study and characterize one important feedback loop within the avian visual system: isthmotectal feedbackloop. The isthmotectal feedback loop consists of the optic tectum: OT) and three nucleus isthmi: Imc, Ipc and SLu. The tectal layer 10 neurons project to ipsilateral Imc, Ipc and SLu in a topographic way. In turn Ipc and SLu send back topographical: local) cholinergic terminals to the OT, whereas Imc sends non-topographical: global) GABAergic projections to the OT, and also to the Ipc and the SLu. We first study the cellular properties of Ipc neurons and found that almost all Ipc cells exhibited spontaneous activity characterized with a barrage of EPSPs and occasional spikes. Further experiments reveal the involvement of GABA in mediating the spontaneous synaptic inputs to the Ipc neurons. Next we investigate the mechanisms of oscillatory bursting in Ipc, which is observed in vivo, by building a model network based on the in vitro experimental results. Our simulation results conclude that strong feedforward excitation and spike-rate adaptation can generate oscillatory bursting in Ipc neuron in response to a constant input. Then we consider the effect of distributed synaptic delays measured within the isthmotectal feedback loop and elucidate that distributed delays can stabilize the system and lead to an increased range of parameters for which the system converges to a stable fixed point. Next we explore the functional features of GABAergic projection from Imc to Ipc and find that Imc has a regulatory role on actions of Ipc neurons in that stimulating Imc can evoke action potentials in Ipc neurons while it also can suppress the firing in Ipc neurons which is generated by somatic current injection. The mechanism of regulatory action is further studied by a two-compartment neuron model. Last, we lay out several open questions in this area which may worth further investigation

Silences, Spikes and Bursts: Three-Part Knot of the Neural Code

When a neuron breaks silence, it can emit action potentials in a number of patterns. Some responses are so sudden and intense that electrophysiologists felt the need to single them out, labeling action potentials emitted at a particularly high frequency with a metonym -- bursts. Is there more to bursts than a figure of speech? After all, sudden bouts of high-frequency firing are expected to occur whenever inputs surge. The burst coding hypothesis advances that the neural code has three syllables: silences, spikes and bursts. We review evidence supporting this ternary code in terms of devoted mechanisms for burst generation, synaptic transmission and synaptic plasticity. We also review the learning and attention theories for which such a triad is beneficial.Comment: 15 pages, 4 figure