Abstract
We show that in an animal model of anxiety the overall excitation, particularly in the infralimbic region of the medial prefrontal cortex (IL), is increased and that the activity ratio between excitatory pyramidal neurons and inhibitory interneurons (AR PN/IN) is shifted towards excitation. The same change in AR PN/IN is evident for wildtype mice, which have been exposed to an anxiety stimulus. We hypothesize, that an elevated activity and the imbalance of excitation (PN) and inhibition (IN) within the neuronal microcircuitry of the prefrontal cortex is responsible for anxiety behaviour and employed optogenetic methods in freely moving mice to verify our findings. Consistent with our hypothesis elevation of pyramidal neuron activity in the infralimbic region of the prefrontal cortex significantly enhanced anxiety levels in several behavioural tasks by shifting the AR PN/IN to excitation, without affecting motor behaviour, thus revealing a novel mechanism by which anxiety is facilitated.
Highlights
Anxiety disorders belong to the most common mental illnesses within the western world affecting a total amount of about 20% of the human population, a lifetime prevalence of nearly 30% and with a steadily increasing occurrence [1,2,3]
One of the key areas involved in the expression of anxiety and fear, beside the hippocampus and the amygdala, is the infalimbic region (IL) of the medial prefrontal cortex [4,5,6,7,8,9], which is the rodent homolog to the anterior cingulate cortex of humans
To test whether disturbed serotonergic neurotransmission might contribute to changes in cortical activity patterns we performed immunohistochemical analyses of neuronal activity in 5-HT1A(-/-) knockout mice (Fig 1), which exhibit enhanced anxiety levels in comparison to wildtype mice (S1 Fig)
Summary
Anxiety disorders belong to the most common mental illnesses within the western world affecting a total amount of about 20% of the human population, a lifetime prevalence of nearly 30% and with a steadily increasing occurrence [1,2,3]. Mainly disturbances in GABAergic neurotransmission have been associated with the manifestation and appearance of anxiety disorders [4,13]. Treatments of choice for generalized anxiety disorders are in many cases benzodiazepine, which act on GABAergic receptors and enhance inhibitory neurotransmission in general [14]. Contradictory result have been obtained, lesions of the mPFC, or inhibition did not affect anxiety behaviour at all or elicit even opposing
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