Reduced GABAergic Inhibition in the Basolateral Amygdala and the Development of Anxiety-Like Behaviors after Mild Traumatic Brain Injury

McLean Hospital/Harvard Medical School, United States of America
PLoS ONE (Impact Factor: 3.23). 07/2014; 9(7):e102627. DOI: 10.1371/journal.pone.0102627


Traumatic brain injury (TBI) is a major public health concern affecting a large number of athletes and military personnel. Individuals suffering from a TBI risk developing anxiety disorders, yet the pathophysiological alterations that result in the development of anxiety disorders have not yet been identified. One region often damaged by a TBI is the basolateral amygdala (BLA); hyperactivity within the BLA is associated with increased expression of anxiety and fear, yet the functional alterations that lead to BLA hyperexcitability after TBI have not been identified. We assessed the functional alterations in inhibitory synaptic transmission in the BLA and one mechanism that modulates excitatory synaptic transmission, the a7 containing nicotinic acetylcholine receptor (a7-nAChR), after mTBI, to shed light on the mechanisms that contribute to increased anxiety-like behaviors. Seven and 30 days after a mild controlled cortical impact (CCI) injury, animals displayed significantly greater anxiety-like behavior. This was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor mediated inhibitory postsynaptic currents (IPSCs). Decreases in the mIPSC amplitude were associated with reduced surface expression of a1, b2, and c2 GABAA receptor subunits. However, significant increases in the surface expression and current mediated by a7-nAChR, were observed, signifying increases in the excitability of principal neurons within the BLA. These results suggest that mTBI causes not only a significant reduction in inhibition in the BLA, but also an increase in neuronal excitability, which may contribute to hyperexcitability and the development of anxiety disorders.

Download full-text


Available from: Eric Michael Prager, Jul 22, 2014
34 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuroimaging identified abnormalities associated with traumatic brain injury (TBI) are but gross indicators that reflect underlying trauma-induced neuropathology at the cellular level. This review examines how cellular pathology relates to neuroimaging findings with the objective of more closely relating how neuroimaging findings reveal underlying neuropathology. Throughout this review an attempt will be made to relate what is directly known from post-mortem microscopic and gross anatomical studies of TBI of all severity levels to the types of lesions and abnormalities observed in contemporary neuroimaging of TBI, with an emphasis on mild traumatic brain injury (mTBI). However, it is impossible to discuss the neuropathology of mTBI without discussing what occurs with more severe injury and viewing pathological changes on some continuum from the mildest to the most severe. Historical milestones in understanding the neuropathology of mTBI are reviewed along with implications for future directions in the examination of neuroimaging and neuropathological correlates of TBI.
    Brain Imaging and Behavior 03/2012; 6(2):108-36. DOI:10.1007/s11682-011-9145-0 · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The 1991 National Health Interview Survey was analysed to describe the incidence of mild and moderate brain injury in the United States. Data were collected from 46 761 households and weighted to reflect all non-institutionalized civilians. The report of one or more occurrences of head injury resulting in loss of consciousness in the previous 12 months was the main outcome measure. Each year an estimated 1.5 million non-institutionalized US civilians sustain a non-fatal brain injury that does not result in institutionalization, a rate of 618 per 100,000 person-years. Motor vehicles were involved in 28% of the brain injuries, sports and physical activity were responsible for 20%, and assaults were responsible for 9%. Medical care was sought by 75% of those with brain injury; 14% were treated in clinics or offices, 35% were treated in emergency departments, and 25% were hospitalized. The risk of medically attended brain injury was highest among three subgroups: teens and young adults, males, and persons with low income who lived alone. The incidence of mild and moderate brain injury in the United States is substantial. The National Health Interview Survey is an important national source of current outpatient brain-injury data.
    Brain Injury 02/1996; 10(1):47-54. DOI:10.1080/026990596124719 · 1.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nearly 64% of people with mild traumatic brain injury (MTBI) experience prolonged symptoms and functional impairments lasting months or years postinjury. Explanations for delayed recovery have varied and lacked a guiding framework, hindering intervention science. Using theory substruction and adapting McLean and associates' biopsychosocial model for chronic pain after trauma, we suggest that perceived psychological stress and associated neurobiological responses may predict risk for functional impairment. This model can be tested using a biopsychosocial approach to determine the interplay of psychological stress and neurobiological responses implicated in functional impairments after MTBI. Testing of this model will advance understanding of pathways to postconcussion syndrome.
    Research and theory for nursing practice 02/2009; 23(1):42-61. DOI:10.1891/1541-6577.23.1.42 · 0.36 Impact Factor
Show more