Editing Classical conditioning (section)

===Neural basis of learning and memory===

Pavlov proposed that conditioning involved a connection between brain centers for conditioned and unconditioned stimuli. His physiological account of conditioning has been abandoned, but classical conditioning continues to be used to study the neural structures and functions that underlie learning and memory. Forms of classical conditioning that are used for this purpose include, among others, [[fear conditioning]], [[eyeblink conditioning]], and the foot contraction conditioning of ''[[Hermissenda crassicornis]]'', a sea-slug. Both fear and eyeblink conditioning involve a neutral stimulus, frequently a tone, becoming paired with an unconditioned stimulus. In the case of eyeblink conditioning, the US is an air-puff, while in fear conditioning the US is threatening or aversive such as a foot shock.

The American neuroscientist [[David A. McCormick]] performed experiments that demonstrated "...discrete regions of the [[cerebellum]] and associated [[brainstem]] areas contain neurons that alter their activity during conditioning – these regions are critical for the acquisition and performance of this simple learning task. It appears that other regions of the brain, including the [[hippocampus]], [[amygdala]], and [[prefrontal cortex]], contribute to the conditioning process, especially when the demands of the task get more complex."<ref>{{cite book |vauthors=Steinmetz JE |chapter-url=https://books.google.com/books?id=RMH8iUZdAFYC |chapter=Neural Basis of Classical Conditioning |title=Encyclopedia of Behavioral Neuroscience |publisher=Academic Press |date=2010 |pages=313–319 |isbn=9780080453965 |access-date=2018-10-01 |archive-date=2021-08-30 |archive-url=https://web.archive.org/web/20210830082457/https://books.google.com/books?id=RMH8iUZdAFYC |url-status=live }}</ref>

Fear and eyeblink conditioning involve generally non overlapping neural circuitry, but share molecular mechanisms. Fear conditioning occurs in the [[basolateral amygdala]], which receives [[Glutamine|glutaminergic]] input directly from thalamic afferents, as well as indirectly from prefrontal projections. The direct projections are sufficient for delay conditioning, but in the case of trace conditioning, where the CS needs to be internally represented despite a lack of external stimulus, indirect pathways are necessary. The [[Anterior cingulate cortex|anterior cingulate]] is one candidate for intermediate trace conditioning, but the hippocampus may also play a major role. Presynaptic activation of [[protein kinase A]] and postsynaptic activation of [[NMDA receptor]]s and its signal transduction pathway are necessary for conditioning related plasticity. [[CREB]] is also necessary for conditioning related [[Neuroplasticity|plasticity]], and it may induce downstream synthesis of proteins necessary for this to occur.<ref>{{cite journal |vauthors=Fanselow MS, Poulos AM |title=The neuroscience of mammalian associative learning |journal=Annual Review of Psychology |volume=56 |issue=1 |pages=207–34 |date=February 2005 |pmid=15709934 |doi=10.1146/annurev.psych.56.091103.070213}}</ref> As NMDA receptors are only activated after an increase in presynaptic [[calcium]](thereby releasing the [[Mg2+]] block), they are a potential coincidence detector that could mediate [[spike timing dependent plasticity]]. STDP constrains LTP to situations where the CS predicts the US, and LTD to the reverse.<ref>{{cite journal |vauthors=Markram H, Gerstner W, Sjöström PJ |title=A history of spike-timing-dependent plasticity |journal=Frontiers in Synaptic Neuroscience |volume=3 |pages=4 |date=2011 |pmid=22007168 |pmc=3187646 |doi=10.3389/fnsyn.2011.00004 |doi-access=free }}</ref>