Effects of distinct excitatory cortical and inhibitory reticular and local thalamic inputs on spindle dynamics
Yazdanbakhsh, Arash; Zikopoulos, Basilis
Based on two distinct thalamocortical (TC) circuits with reciprocal components in
primates, we developed models of core, matrix, and mixed TC loops. The core TC circuit,
prevalent in sensory thalamus, drives activity focally in the middle cortical layers and gets
feedback through small modulatory cortical axon terminals from pyramidal neurons in layer 6
(L6). The matrix TC circuit, can drive activity in high-order thalamus, through large axon
terminals from cortical layer 5 (L5) pyramidal neurons and includes broad thalamic feedback to
the superficial cortical layers. The inhibitory thalamic reticular nucleus (TRN) intercepts all TC
communication and is situated strategically between the thalamus and cortex. We used distinct
core and matrix TRN components to engage cortico-TRN and thalamo-TRN loops in pure core,
pure matrix or mix TC loops to investigate the functional consequences of different ratios of core
and matrix node connectivity contribution to spindle dynamics. Our models comprised more
numerous projections from cortical L6 pyramidal neurons to TRN and thalamus, but we also
included direct L5 projections to matrix TRN (L5-TRN) and thalamus with a range of density of
L5-TRN, starting from zero. Based on our rate-based model circuit we found: a) increased local
inhibition in the thalamus or b) increased TRN inhibition of core and matrix thalamic neurons
enhances spindle generation and sustains spindle activity for longer periods; c) a more diffuse
nature of spindles in matrix compared to core, with the mix type showing intermediate properties
in agreement with hypotheses that spindles can be classified in core-generated, matrix-generated
or mixed types, depending on the neuroanatomy of pathways involved in their generation; d) the
involvement of L5-TRN projection enhances the spindle generation and propagation; and e)
spindle power can be modulated based on the level of cortical feedback and involvement in
model core vs. matrix. Our rate-based model tested the impact of different ratios and
specializations of neuroanatomical connectivity at multiple nodes of the TC circuit in spindle
dynamics. Our simulations provide detailed metrics for shifts in the engagement of distinct TRN,
core, and matrix circuits underlying typical sleep spindle generation and states of vigilance. This
work can help establish a framework to study disruption of TC-TRN circuit balance in seizures,
atypical sensory reactivity, and deficits in sleep and attentional gating seen in autism and
schizophrenia.
↧