Transcript 5104_b4
Triad of systems mediate response to stress Color-enhanced image of the expression of mRNA encoding (a) glucocorticoid receptor (GR) and (b) mineralocorticoid receptor (MR) in coronal sections of the fetal guinea pig brain. Trends Endo Metab 13: 2002 News and Views Nature Neuroscience 8, 261 - 262 (2005) Controlling stress: how the brain protects itself from depression Trevor W Robbins University of Cambridge, Cambridge, UK. [email protected] Having control over a stressful situation can reduce its negative physiological and cognitive consequences. In this issue, a new study in rats suggests that descending inputs from the prefrontal cortex to the serotonergic midbrain signal the controllability of stress. Figure 1. Sensing control over stress. The dorsal raphé nucleus (DRN) is a major source of ascending serotonergic (5-HT) input to forebrain structures such as the neocortex, the dorsal (DS) and ventral (VS) striatum, and the amygdala (Amyg)11. The ventromedial prefrontal cortex (PFC) (including the infralimbic and prelimbic regions in the rat brain) is a major source of descending input to the DRN5, 6. Stressors can elevate the activity of 5-HT neurons in the DRN through a number of other inputs to this structure (not shown)3. One potential consequence of uncontrollable, chronic stress is a dysregulation of activity in the ascending 5-HT system3, which likely impairs information processing in its diverse terminal domains, possibly leading to depression and other affective disorders. By sensing the capacity to exert control over stress through instrumental behavior, the mPFCv may modulate the activity of 5-HT neurons in the DRN through descending excitatory afferents (purple), either directly or through inhibitory GABAergic (G) THE STRESSED HIPPOCAMPUS, SYNAPTIC PLASTICITY AND LOST MEMORIES Jeansok J. Kim & David M. Diamond Nature Reviews Neuroscience 3, 453-462 (2002) Stress is a biologically significant factor that, by altering brain cell properties, can disturb cognitive processes such as learning and memory, and consequently limit the quality of human life. Extensive rodent and human research has shown that the hippocampus is not only crucially involved in memory formation, but is also highly sensitive to stress. So, the study of stressinduced cognitive and neurobiological sequelae in animal models might provide valuable insight into the mnemonic mechanisms that are vulnerable to stress. Here, we provide an overview of the neurobiology of stress–memory interactions, and present a neural–endocrine model to explain how stress modifies hippocampal functioning. Various effects on learning an memory as a function of the magnitude of stress Stress impairs memory Long term potentiation induced by tetanic stimulation of the Schaffer collateral excitatory pathway in a hippocampal slice Uncontrollable restraint–tailshock stress impairs LTP in the hippocampus in vitro. a | Schematic diagram of a transverse hippocampal slice, showing the arrangement of recording and stimulating electrodes. b | Post-tetanus population field potentials recorded from the cell-body layer of the CA1 field in response to test stimulation of the Schaffer collateral/commissural fibres (Sch). Tetanizing stimulation long-term potentiation induced in hippocampal slices prepared from unstressed control rats but not from stressed rats. Exposing a rat to a natural predator (a cat) impairs cognitive and electrophysiological measures of hippocampal functioning. A rat with no previous exposure to a cat shows an innate 'freezing' (fear) response in the presence of a cat. a | After 75 minutes of exposure to the cat, rats showed a complete suppression of synaptic plasticity (primed-burst potentiation, or PBP) in area CA1 of the hippocampus (bar labelled Cat). By contrast, rats placed in the chamber for 75 minutes without the cat (Chamber) showed as much PBP as rats that were undisturbed in their home environment (Home). b | Rats have excellent spatial working memory under non-stress conditions (WM-Home) when tested in the radial-arm water maze. However, rats that were exposed to a cat showed a selective impairment of hippocampus-dependent working memory (WM-Cat), with no adverse effect of stress on hippocampus-independent reference memory (RM-Cat).