Fos-like immunoreactivity in the brain associated with freezing or escape induced by inhibition of either glutamic acid decarboxylase or GABAA receptors in the dorsal periaqueductal gray.
GABAergic neurons exert tonic control over the neural substrates of aversion in the dorsal periaqueductal gray (dPAG). It has been shown that electrical stimulation of this region at freezing or escape thresholds activates different neural circuits in the brain. Since electrical stimulation activates cell bodies and fibers of passage, it is necessary to use chemical stimulation that activates only post-synaptic receptors. To investigate this issue further, reduction of GABA transmission was performed with local injections of either the GABA-A receptor antagonist bicuculline or the glutamic acid decarboxylase (GAD) inhibitor semicarbazide into the dorsolateral periaqueductal gray (dlPAG). Local infusions of semicarbazide (5.0 microg/0.2 microl) or bicuculline (40 ng/0.2 microl) into this region caused freezing and escape, respectively. The results obtained showed that freezing behavior induced by semicarbazide was associated with an increase in Fos expression in the laterodorsal nucleus of the thalamus (LD) and ventrolateral periaqueductal gray (vlPAG), while bicuculline-induced escape was related to widespread increase in Fos labeling, notably in the columns of the periaqueductal gray, hypothalamus nuclei, the central amygdaloid nucleus (Ce), the LD, the cuneiform nucleus (CnF) and the locus coeruleus (LC). Thus, the present data support the notion that freezing and escape behaviors induced by GABA blockade in the dlPAG are neurally segregated: freezing activates only structures that are mainly involved in sensory processing, and bicuculline-induced escape activates structures involved in both sensory processing and motor output of defensive behavior. Therefore, the freezing elicited by activation of dlPAG appears to be related to the acquisition of aversive information, whereas most brain structures involved in the defense reaction are recruited during escape.
Laboratório de Psicobiologia, FFCLRP-USP, Av. Bandeirantes 3900, 14049-901, Ribeirão Preto, SP, Brasil.
Karina Genaro
KG
Borelli
Cristina
C
Ferreira-Netto
Norberto Cysne
NC
Coimbra
Marcus Lira
ML
Brandão
D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists / Q000008:administration & dosage; D005968:Glutamate Decarboxylase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012663:Semicarbazides / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011963:Receptors, GABA-A; D012663:Semicarbazides; C010059:carbamylhydrazine; D005968:Glutamate Decarboxylase; D001640:Bicuculline