Thalamocortical network interruption: A fresh view for migraine symptoms

The thalamus and cerebral cortex are intimately linked through strong topographical connections, not only from the thalamus to the cortex, but also from the cortex back to the thalamus. As in many parts of the brain, the basic circuit of thalamocortical connectivity is relatively simple, although intracortical and corticocortical connectivity provides a high level of complexity. One of the basic operations of the thalamocortical network is the generation of rhythmic oscillations, which are now relatively well understood. In the normal brain, these thalamocortical oscillations typically occur during sleep, although their pathological counterparts may appear as seizures during sleep or waking. Unfortunately, the normal function of reciprocal thalamocortical connectivity during the waking state is still unknown. Even so, focused research is yielding insights into the properties of each of the cellular and synaptic components of these networks and how they interact to perform circuitwide operations.

Download Full-text

0158 Loss of Connexin 36 Elicits Abnormalities in Thalamocortical Network Activity Relevant to Neuropsychiatric Disorders

SLEEP ◽

10.1093/sleep/zsaa056.156 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A62-A62

Author(s):

J M McNally ◽

S Thankachan ◽

D S Uygun ◽

R Basheer

Keyword(s):

Gap Junctions ◽

Neuropsychiatric Disorders ◽

Gamma Band ◽

Network Activity ◽

Light Phase ◽

Eeg Activity ◽

Connexin 36 ◽

Thalamocortical Network ◽

Gamma Band Activity ◽

Band Activity

Abstract Introduction Neuronal gap-junctions are extensively expressed in mammalian forebrain and suggested to contribute to state-regulation and thalamocortical network activity. However, the physiological role of gap-junctions on these processes remains poorly understood. Connexin-36 (Cxn36) is highly expressed in the brain, representing a mechanism for electrical coupling of inhibitory neurons. We examined the effects of global Cnx36 deletion on sleep/wake and spontaneous and evoked EEG activity. Methods We recorded in vivo EEG/EMG in Cxn36KO mice and littermate controls. Electrodes were stereotaxically implanted above frontal cortices. We analyzed sleep/wake states and algorithmically detected sleep spindles over 24 hours. Mice underwent auditory stimulation paradigms including the auditory steady state response (ASSR; 1 second train 20-50Hz clicks, 100 reps., 85dB) and mismatch negativity (MMN; 2.5kHz standard 90%, 10kHz deviant 10%, 300ms ISI, 90dB). Social behavior and investigation-evoked EEG activity were also assessed via the social habituation task (repeated 5 min exposures to novel mouse). Results Cnx36KO mice exhibited limited sleep/wake abnormalities (n=7/group). Power spectra of EEG revealed significant impairments in spontaneous gamma-band activity (30-80Hz; All States, Light & Dark Phases), and beta activity (15-25Hz; All States, Light Phase). Sigma activity (10-15Hz) was significantly decreased (NREM and REM, Light phase). This was particularly pronounced during NREM-REM transitions. Despite no changes in spindle density, both spindle amplitude and duration were significantly decreased in Cnx36KOs. Cxn36KOs exhibited a blunted gamma-band response to acute ketamine (15mg/kg; IP), impaired 30 & 40Hz ASSR, and an abnormal response in the MMN task (decrease ERP peak amplitude & gamma). Finally, Cxn36KO mice exhibit impaired social habituation and significantly decreased investigation evoked slow gamma-band activity (30 - 55Hz). Conclusion Our data suggest Cxn36 plays a critical role in regulating thalamocortical network activity. Further, impairments in Cnx36KO mice reflect abnormalities in neuropsychiatric disorders, including schizophrenia, implicating Cnx36 containing gap junctions as a novel therapeutic target. Support Research supported by VA CDA Award BX002130 (JMM), VA Merit Awards BX004500 (JMM), BX001404 (RB), and NIMH RO1 MH39683 (Ritchie E. Brown).

Download Full-text

Seizure Detection and Network Dynamics of Generalized Convulsive Seizures: Towards Rational Designing of Closed-Loop Neuromodulation

Neuroscience Journal ◽

10.1155/2017/9606213 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Puneet Dheer ◽

Ganne Chaitanya ◽

Diana Pizarro ◽

Rosana Esteller ◽

Kaushik Majumdar ◽

...

Keyword(s):

Closed Loop ◽

Network Dynamics ◽

Seizure Detection ◽

Line Length ◽

Detection Methods ◽

Sprague Dawley ◽

Subcortical Structures ◽

Clonic Seizures ◽

Thalamocortical Network ◽

Convulsive Seizures

Objective. Studies have demonstrated the utility of closed-loop neuromodulation in treating focal onset seizures. There is an utmost need of neurostimulation therapy for generalized tonic-clonic seizures. The study goals are to map the thalamocortical network dynamics during the generalized convulsive seizures and identify targets for reliable seizure detection. Methods. Local field potentials were recorded from bilateral cortex, hippocampi, and centromedian thalami in Sprague-Dawley rats. Pentylenetetrazol was used to induce multiple convulsive seizures. The performances of two automated seizure detection methods (line length and P-operators) as a function of different cortical and subcortical structures were estimated. Multiple linear correlations-Granger’s Causality was used to determine the effective connectivity. Results. Of the 29 generalized tonic-clonic seizures analyzed, line length detected 100% of seizures in all the channels while the P-operator detected only 35% of seizures. The detection latencies were shortest in the thalamus in comparison to the cortex. There was a decrease in amplitude correlation within the thalamocortical network during the seizure, and flow of information was decreased from thalamus to hippocampal-parietal nodes. Significance. The preclinical study confirms thalamus as a superior target for automated detection of generalized seizures and modulation of synchrony to increase coupling may be a strategy to abate seizures.

Download Full-text