Detailed Characterization of Synaptic Inputs Reveals the Mechanisms Underlying Spontaneous Spiking in Recurrent Neural Networks

Keskeiset käsitteet

Postsynaptic spiking during spontaneous recurrent network activity is primarily driven by rapid and brief changes in the balance of excitatory and inhibitory synaptic inputs, with a key role for a few strongly connected inhibitory hub neurons.

Tiivistelmä

The study developed a novel experimental platform and analytical procedures to reconstruct the excitatory and inhibitory synaptic input activity experienced by individual neurons during periods of spontaneous spiking in recurrent neuronal networks.
Key findings:

Spiking of individual neurons was dominantly controlled by a few strong incoming connections, with inhibitory inputs playing a particularly important role.
Neuronal spiking was partially governed by rapid and brief changes in the balance of excitatory and inhibitory synaptic inputs, with the peak of the E/I ratio increase coinciding precisely with the action potential trigger time.
The network contained a few key inhibitory hub cells with high spike rates, strong synapses, and fast action potential propagation that exerted a dominant influence on network activity.
The results suggest that the emergence of favorable dynamical regimes with rapid membrane potential fluctuations is an inherent property of cortical networks, enabled by the specific circuit architecture.

Tilastot

"Neurons typically receive a continuous bombardment by orchestrated excitatory and inhibitory synaptic inputs, which ultimately determines postsynaptic spiking."
"Theoretical work suggests that balanced networks can potentially assume multiple different dynamical states."
"Across a total of 14 patched putatively excitatory cells, 142 incoming connections were identified (mean = 10.1 ± 5.2 s.d.; min = 3, max = 20 connections per cell)."
"Inhibitory cells displayed higher spike rates and conductances and lower onset latencies compared to excitatory cells."

Lainaukset

"Balanced network theory predicts dynamical regimes governed by small and rapid input fluctuation and featuring a fast neuronal responsiveness."
"Our findings – obtained in self-organized neuronal cultures – suggest that the emergence of these favorable regimes and associated network architectures is an inherent property of cortical networks in general."
"A few key inhibitory cells were in a unique position to coordinate network activity by exerting fast and strong effects through an extensive network of outgoing connections."

Tärkeimmät oivallukset

Parallel reconstruction of the excitatory and inhibitory inputs received by single neurons reveals the synaptic basis of recurrent spiking

by Bartram,J., ... klo www.biorxiv.org 01-08-2023

https://www.biorxiv.org/content/10.1101/2023.01.06.523018v3

Syvällisempiä Kysymyksiä

How do the synaptic mechanisms underlying spontaneous spiking in recurrent networks differ in vivo compared to the in vitro neuronal cultures examined in this study?

The synaptic mechanisms underlying spontaneous spiking in recurrent networks exhibit notable differences between in vivo and in vitro environments. In vivo, neurons are subject to a complex array of sensory inputs and modulatory influences from various brain regions, leading to a more dynamic and context-dependent synaptic environment. This results in a greater variability in synaptic strength and a more intricate balance of excitation and inhibition, influenced by factors such as neuromodulation and the presence of diverse neurotransmitter systems. In contrast, the in vitro neuronal cultures examined in this study provide a controlled environment where spontaneous recurrent activity is primarily self-generated, lacking the external inputs and modulatory influences present in vivo.
In the in vitro setting, the study found that postsynaptic spiking was closely associated with rapid fluctuations in the excitation-inhibition (E/I) balance, often driven by a few dominant inhibitory connections from hub neurons. This contrasts with in vivo conditions, where the E/I balance may be more stable and influenced by ongoing sensory processing and behavioral states. Additionally, the study highlights that the synaptic architecture in vitro can lead to a more predictable and uniform response to synaptic inputs, whereas in vivo networks may exhibit greater variability and adaptability in their spiking responses due to the influence of external stimuli and network dynamics.

What are the potential implications of the identified network architecture, with a few dominant inhibitory hub cells, for information processing and cognitive functions?

The identified network architecture, characterized by a few dominant inhibitory hub cells, has significant implications for information processing and cognitive functions. These hub cells, which exhibit high spike rates and strong synaptic connections, play a crucial role in coordinating network activity. Their ability to exert rapid and robust inhibitory control can enhance the precision and timing of neuronal firing across the network, facilitating synchronized activity that is essential for various cognitive processes, such as attention, memory, and decision-making.
Moreover, the presence of these key inhibitory hubs suggests a mechanism for efficient information filtering and processing. By selectively inhibiting less relevant or redundant neuronal activity, these hub cells can enhance the signal-to-noise ratio within the network, allowing for more effective encoding and retrieval of information. This architecture may also support the emergence of oscillatory dynamics, which are often associated with cognitive functions such as working memory and sensory perception. Overall, the dominance of specific inhibitory cells in shaping network dynamics underscores the importance of inhibitory control in maintaining the balance between excitation and inhibition, which is vital for optimal cognitive functioning.

Could the rapid and brief changes in the excitation-inhibition balance that trigger spiking be leveraged for developing novel brain-computer interface or neural prosthetic technologies?

Yes, the rapid and brief changes in the excitation-inhibition (E/I) balance that trigger spiking present a promising avenue for the development of novel brain-computer interface (BCI) and neural prosthetic technologies. Understanding the precise mechanisms by which these fluctuations influence neuronal firing can inform the design of devices that interact with the brain's natural signaling processes.
For instance, BCIs could be engineered to detect and respond to these rapid E/I changes, allowing for real-time modulation of neuronal activity. By harnessing the dynamics of E/I balance, such technologies could enhance the precision of neural signal decoding, improving the control of prosthetic limbs or communication devices for individuals with motor impairments. Additionally, the ability to manipulate E/I balance through targeted stimulation could facilitate the restoration of lost functions or the enhancement of cognitive processes, such as memory and learning.
Furthermore, insights gained from the study's findings on the role of inhibitory hub cells could lead to the development of more sophisticated neural interfaces that mimic the natural inhibitory control mechanisms of the brain. This could result in more effective and adaptive BCIs that not only interpret neural signals but also modulate them in a way that aligns with the brain's intrinsic dynamics, ultimately improving the efficacy of neural prosthetics and enhancing user experience.