Fear

Cross references:   Stress      Pain    

NOTES:   
    Although Stress ,  Fear and  Pain are not identical, there's enough similarity between them that it's informative to extrapolate from one to the others.   
    I've copied a section from the 'Brain from Top to Bottom (BTB)' website, below.  More than anything else, I'm interested in the  Direct Serotonin Pathway  , since that seems to be the most relevant to the out-of-control young men I encounter in the classroom. 


THE TWO PATHWAYS OF FEAR  (BTB) 

http://thebrain.mcgill.ca/flash/a/a_04/a_04_cr/a_04_cr_peu/a_04_cr_peu.html       
THE AMYGDALA AND ITS ALLIES

     When the brain receives a sensory stimulus indicating a danger, it is routed first to the Thalamus. From there, the information is sent out over two parallel pathways: the thalamo-amygdala pathway (the "short route") and the thalamo-cortico-amygdala pathway (the "long route").  
    The short route conveys a fast, rough impression of the situation, because it is a sub-cortical pathway in which no cognition is involved. This pathway activates the amygdala which, through its central nucleus, generates emotional responses before any perceptual integration has even occurred and before the mind can form a complete representation of the stimulus.

    Subsequently, the information that has travelled via the long route and been processed in the cortex reaches the amygdala and tells it whether or not the stimulus represents a real threat. To provide this assessment, various levels of cortical processing are required.

 

    First, the various modalities of the perceived object are processed by the primary sensory cortex. Then the unimodal associative cortex provides the amygdala with a representation of the object. At an even higher level of analysis, the polymodal associative cortex conceptualizes the object and also informs the amygdala about it. This elaborate representation of the object is then compared with the contents of explicit memory by means of the hippocampus, which also communicates closely with the amygdala.


    The hippocampus is the structure that supports the explicit memory required to learn about the dangerousness of an object or situation in the first place. The hippocampus is also especially sensitive to the encoding of the context associated with an aversive experience. It is because of the hippocampus that not only can a stimulus become a source of conditioned fear, but so can all the objects surrounding it and the situation or location in which it occurs.

    The imminent presence of a danger then performs the task of activating the amygdala, whose discharge patterns in turn activate the efferent structures responsible for physical manifestations of fear, such as increased heart rate and blood pressure, sweaty hands, dry mouth, and tense muscles.

    The parallel operation of our explicit (hippocampal) and implicit (amygdalic) memory systems explains why we do not remember traumas experienced very early in our lives. At that age, the hippocampus is still immature, while the amygdala is already able to record unconscious memories. Early childhood traumas can disturb the mental and behavioural functions of adults by mechanisms that they cannot access consciously.   
    See:  Amygdala    and  Hippocampus    . 

My comments
    1.  Since this explanation does not consider the  Paraventricular nucleus (PVN)  of the Hypothalamus, Corticotropin-releasing hormone (CRH)  , the anterior  Pituitary GlandACTH  the  Adrenal CortexCortisol or the  HPA Axis  , it can't be said to consider the  Direct Cortisol Pathway  .  
    2.  Although this explanation does mention both the  Amygdala  and the  Hippocampus  , it does not mention either the   Dorsal Raphe Nucleus   or  Serotonin , so it can't be said to consider the complete  Direct Serotonin Pathway either.   
    3.  The "long route" described in this article passes through the cortex.  Neither the  Direct Cortisol Pathway  nor the Direct Serotonin Pathway pass through the cortex.  Both are strictly subcortical.     
    4.  The "short route" described in this article does not pass through the cortex.  It is strictly subcortical.  Therefore, the Direct Cortisol Pathway  and the Direct Serotonin Pathway  considered together can be thought of as a more detailed description of part of the "short route". 
    5.  Since sensory input converges on the Thalamus, it's possible that sensory input to the Thalamus initiates both the  Direct Cortisol Pathway  and the Direct Serotonin Pathway  .  However, this isn't necessarily the case.  Since one of the major roles of   Cortisol  is to regulate the level of circulating Glucose , perhaps an as yet unidentified glucose sensor controls the release of   Corticotropin-releasing hormone (CRH)  by the Paraventricular nucleus (PVN)  and the resulting cascade of the Direct Cortisol Pathway  then controls, or at least influences,  the Direct Serotonin Pathway .          


1987    
Defense reaction elicited by injection of GABA antagonists and synthesis inhibitors into the posterior hypothalamus in rats.   
http://www.ncbi.nlm.nih.gov/pubmed/3037412   
    "Blockade of gamma-aminobutyric acid (GABA) in the posterior hypothalamic nucleus elicits cardiorespiratory stimulation in anesthetized rats. The present study was conducted to test the hypothesis that blockade of GABA in this cardiostimulatory area of the posterior hypothalamus in conscious animals would elicit a defense reaction characterised by a "fight or flight" response. Blockade of GABA was achieved by injecting bicuculline methiodide (BMI 1-25 ng) and picrotoxin (4-100 ng), two post-synaptic GABA antagonists and isoniazid (INH 35 and 70 micrograms), an inhibitor of the synthesis of GABA, bilaterally into the posterior hypothalamus through chronically implanted microinjection cannulae. All three drugs produced dose-dependent increases in locomotor activity, suggesting an "escape" reaction which was quantified as number of crossings and rearings. The effects of bicuculline and picrotoxin appeared immediately after the injection while those of isoniazid appeared much more slowly, attaining peak effects 24 +/- 1 min after injection. Injection of either strychnine (38 ng) into the posterior hypothalamus or bicuculline into the lateral hypothalamic area (LHA) or the dorso-medial/ventro-medial hypothalamus (DMH/VMH) did not elicit a significant increase in locomotor behavior. These results suggest that both the physiological and locomotor components of the hypothalamic defense reaction may be under tonic GABAergic inhibition in the region of the posterior hypothalamus."      
    165  Related citations:   
http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=3037412   
    17  Cited by's: 
http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_citedin&from_uid=3037412   


2004     
Defense reaction mediated by NMDA mechanisms in the inferior colliculus is modulated by GABAergic nigro-collicular pathways.     
http://www.ncbi.nlm.nih.gov/pubmed/14746929   
    "Electrical stimulation of the inferior colliculus (IC) causes a behavioral activation together with autonomic responses similar to fear reactions to threatening situations. GABAergic mechanisms exert a tonic inhibitory control on the neural substrates of aversion in the IC insofar as local injections of GABA agonists or antagonists inhibit or mimic these defensive behaviors, respectively. Recently, we have shown that systemic injections of the GABA-A receptor agonist muscimol unexpectedly enhanced the freezing and escape responses provoked by gradual increases in the intensity of the electrical stimulation of the IC. Taking into account that the neural circuits mediated by excitatory amino acids (EAA) in the IC may be responsible for the integration of fear states, in the present study we examined whether the defensive behavior induced by local injections of NMDA into the IC is influenced by prior treatment with systemic muscimol and also whether this GABAergic control could be exerted by GABAergic fibers that project to the inferior colliculus from the substantia nigra pars reticulata (SNpr). Rats were implanted with two guide-cannulae aimed at the IC and SNpr through which drug microinfusions with glass micropipette could be made with reduced brain damage. One week after surgery, the animals received either NMDA (7 nmol/0.2 microl) or saline into the IC and were placed into the middle of an enclosure where behavioral responses such as freezing, crossings, jumping, rearing, and turnings could be measured as an indirect index of unconditioned fear. These animals were pretreated either with saline or muscimol (0.5 mg/kg, IP) or with brain injections of saline or muscimol (1 nmol/0.2 ìl into SNpr). NMDA applied into the IC produced a behavioral activation with significant increases in all behavioral measures. IP injections of muscimol or into the SNpr enhanced the defense reaction caused by microinjections of NMDA into the IC. These findings give support to the idea that unconditioned defensive responses generated in the IC may be mediated by NMDA mechanisms. Additionally, a reduction of the inhibitory control exerted by nigrocollicular GABAergic neurons seems to be responsible for the unexpected pro-aversive action of systemic injections of muscimol on the neural substrates of aversion mediated by NMDA in the IC."     
    726 Related citations: 
http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=14746929  
    2 Cited by's. 


2008    489<1206  
Gabaergic mechanisms of hypothalamic nuclei in the expression of conditioned fear. 
http://www.ncbi.nlm.nih.gov/pubmed/18634894   
    "The amygdala, the dorsal periaqueductal gray (dPAG), and the medial hypothalamus have long been recognized to be a neural system responsible for the generation and elaboration of unconditioned fear in the brain.  
    It is also well known that this neural substrate is under a tonic inhibitory control exerted by GABA mechanisms. However, whereas there is a growing body of evidence to suggest that the amygdala and dPAG are also able to integrate conditioned fear, it is still unclear, however, how the distinct hypothalamic nuclei participate in fear conditioning.  
    In this work we aimed to examine the extent to which the gabaergic mechanisms of this brain region are involved in conditioned fear using the fear-potentiated startle (FPS). Muscimol, a GABA-A receptor agonist, and semicarbazide, an inhibitor of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD), were used as an enhancer and inhibitor of the GABA mechanisms, respectively.  
    Muscimol and semicarbazide were injected into the anterior hypothalamus (AHN), the dorsomedial part of the ventromedial nucleus (VMHDM), the dorsomedial (DMH) or the dorsal premammillary (PMD) nuclei of male Wistar rats before test sessions of the fear conditioning paradigm.  
    The injections into the DMH and PMD did not produce any significant effects on FPS. On the other hand, muscimol injections into the AHN and VMHDM caused significant reduction in FPS.  
    These results indicate that injections of muscimol and semicarbazide into the DMH and PMD fail to change the FPS, whereas the  
    enhancement of the GABA transmission in the AHN and VMHDM produces a reduction of the conditioned fear responses. On the other hand, the  
    inhibition of this transmission led to an increase of this conditioned response in the AHN.  
    Thus, whereas DMH and PMD are known to be part of the caudal-most region of the medial hypothalamic defensive system, which integrates unconditioned fear,  
    systems mediating conditioned fear select the AHN and VMHDM nuclei that belong to the rostral-most portion of the hypothalamic defense area. Thus, distinct subsets of neurons in the hypothalamus could mediate different aspects of the defensive responses."     
    724 Related citations: 
http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=18634894   
    2 Cited by's.     





BwoF  Fear 
150726 - 1128 









Comments