Parvalbumin fast-spiking interneurons are selectively altered by paediatric traumatic brain injury

Joshua Nichols, George Reed Bjorklund, Jason Newbern, Trent R Anderson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Key points: Traumatic brain injury (TBI) in children remains a leading cause of death and disability and it remains poorly understood why children have worse outcomes and longer recover times. TBI has shown to alter cortical excitability and inhibitory drive onto excitatory neurons, yet few studies have directly examined changes to cortical interneurons. This is addressed in the present study using a clinically relevant model of severe TBI (controlled cortical impact) in interneuron cell type specific Cre-dependent mice. Mice subjected to controlled cortical impact exhibit specific loss of parvalbumin (PV) but not somatostatin immunoreactivity and cell density in the peri-injury zone. PV interneurons are primarily of a fast-spiking (FS) phenotype that persisted in the peri-injury zone but received less frequent inhibitory and stronger excitatory post-synaptic currents. The targeted loss of PV-FS interneurons appears to be distinct from previous reports in adult mice suggesting that TBI-induced pathophysiology is dependent on the age at time of impact. Abstract: Paediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Traditionally, ongoing neurodevelopment and neuroplasticity have been considered to confer children with an advantage following TBI. However, recent findings indicate that the paediatric brain may be more sensitive to brain injury. Inhibitory interneurons are essential for proper cortical function and are implicated in the pathophysiology of TBI, yet few studies have directly investigated TBI-induced changes to interneurons themselves. Accordingly, in the present study, we examine how inhibitory neurons are altered following controlled cortical impact (CCI) in juvenile mice with targeted Cre-dependent fluorescence labelling of interneurons (Vgat:Cre/Ai9 and PV:Cre/Ai6). Although CCI failed to alter the number of excitatory neurons or somatostatin-expressing interneurons in the peri-injury zone, it significantly decreased the density of parvalbumin (PV) immunoreactive cells by 71%. However, PV:Cre/Ai6 mice subjected to CCI showed a lower extent of fluorescence labelled cell loss. PV interneurons are predominantly of a fast-spiking (FS) phenotype and, when recorded electrophysiologically from the peri-injury zone, exhibited intrinsic properties similar to those of control neurons. Synaptically, CCI induced a decrease in inhibitory drive onto FS interneurons combined with an increase in the strength of excitatory events. The results of the present study indicate that CCI induced both a loss of PV interneurons and an even greater loss of PV expression. This suggests caution is required when interpreting changes in PV immunoreactivity alone as direct evidence of interneuronal loss. Furthermore, in contrast to reports in adults, TBI in the paediatric brain selectively alters PV-FS interneurons, primarily resulting in a loss of interneuronal inhibition.

Original languageEnglish (US)
Pages (from-to)1277-1293
Number of pages17
JournalJournal of Physiology
Volume596
Issue number7
DOIs
StatePublished - Apr 1 2018

Fingerprint

Parvalbumins
Interneurons
Pediatrics
Neurons
Wounds and Injuries
Traumatic Brain Injury
Cause of Death
Fluorescence
Phenotype
Neuronal Plasticity
Somatostatin-Secreting Cells
Brain
Somatostatin
Brain Injuries
Cell Count

Keywords

  • cortex
  • interneuron
  • parvalbumin
  • pediatric
  • traumatic brain injury

ASJC Scopus subject areas

  • Physiology

Cite this

Parvalbumin fast-spiking interneurons are selectively altered by paediatric traumatic brain injury. / Nichols, Joshua; Bjorklund, George Reed; Newbern, Jason; Anderson, Trent R.

In: Journal of Physiology, Vol. 596, No. 7, 01.04.2018, p. 1277-1293.

Research output: Contribution to journalArticle

Nichols, Joshua ; Bjorklund, George Reed ; Newbern, Jason ; Anderson, Trent R. / Parvalbumin fast-spiking interneurons are selectively altered by paediatric traumatic brain injury. In: Journal of Physiology. 2018 ; Vol. 596, No. 7. pp. 1277-1293.
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