in their companion article , tononi and cirelli argue that i have missed the big picture by conflating questions of sleep function with the underlying mechanisms . as i have discussed elsewhere
[ 2 , 3 ] , understanding sleep function is of central importance to biology .
any theory of sleep function must also grapple with universal traits of sleep , some of which were enumerated in their response .
there are other theories of sleep function and many of the theoretical arguments made in support of shy ( e.g. , a need for offline states , sleep homeostasis , and brain metabolism ) apply to them .
my position is that this evaluation must always include a discussion of mechanisms , because they can not be disentangled from functional questions .  
the underlying message from tononi and cirelli is that what really matters is the  
the end result  [ 1 , page 4 ] rather than how you get there .
i find this an odd position to take and a backward step in our pursuit of sleep function .
the goal of science is to understand how nature works . that includes an empirical pursuit of physical mechanisms .
scientists should therefore be skeptical of any theory of sleep function that fails to elucidate the underlying mechanisms that govern the proposed function . in this regard ,
the proponents of shy are in an indefensible position when they argue that the mechanisms have   no bearing on whether the core claim of shy is true or false  [ 1 , page 3 ] .
they have bearing because if the underlying mechanisms are not sleep dependent then the theory is wrong .
incidentally , the theory is also wrong if the proposed mechanisms do not exist . while it may be true that these mechanisms are complex and perhaps different in different species , that is not a reason to ignore them . on the contrary , that is a reason to explore them .
. indeed , i do find shy confusing because the proposed mechanisms ( to date ) seem inconsistent with what is actually known about synaptic plasticity .
moreover , their imprecise terminology fogs the issue . they claim that they never meant that the potentiation in wakefulness is hebbian ( i.e. , some form of ltp ) , yet it is difficult to draw any other conclusion based on their own words . their liberal and interchangeable use of the words  long - term potentiation  ,  ltp ,  or 
this is because  ltp  is not short - hand for  stronger synapse ;  it has a precise meaning and commonly refers to hebbian processes . in their rebuttal
, they back peddle from their past specific language regarding the significance of neuromodulator release and the expression of plasticity molecules in shy .
there is , however , little ambiguity in their original description of how these events purportedly promote ltp ( or ltp - like events ) during wake versus sleep [ 4 , 5 ] .   
the concepts and terminology of synaptic homeostasis and scaling predate shy   and there is simply no mistaking the broad similarities between synaptic scaling and what is described in shy .
for example , here is a more complete excerpt from tononi and cirelli .     like activity - dependent synaptic scaling ( emphasis added ) , however , sleep - dependent downscaling would affect most or all of a neuron 's synapses . in this respect , downscaling is conceptually different from long - term depression , which affects select groups of synapses , or depotentiation , which affects only recently potentiated ones 
therefore , their use of these terms , if in fact they mean something else , is perplexing . the distinctions they make between their version of downscaling and scaling proper are welcome , but quite subtle when compared to the overall similarities .
for example , synaptic homeostasis is not only manifested at the level of firing rates as implied by tononi and cirelli .
that is one outcome of a homeostatic adjustment of synaptic weights in a network , as measured , for example , by mepscs [ 7 , 8 ] .
this point seems moot , since tononi and cirelli cite changes in firing rates and mepscs as evidence of shy [ 9 , 10 ] .    in the end , it really does not matter what new name they give to their process ( or set of processes ) that weakens synapses .
the point i was making , and which they missed , is that any form of plasticity ( especially if possibly novel ) should be examined through the prism of known facts about hebbian and non - hebbian plasticity .
case in point : i never stated that the  downscaling  of shy is identical to synaptic scaling as currently understood in the field .
i instead argued that since the concepts of scaling figure prominently in shy , and because scaling is an accepted means of globally adjusting synaptic weight , it is logical to examine the claims of shy based on what is known about synaptic scaling .
 synaptic renormalization  from synaptic scaling , but this name change does not inoculate shy against scrutiny .
  the veracity and validity of a scientific theory is not solely determined by the amount of data piled on one side of a scale .
it is also determined by a careful examination of each piece of evidence , pro and con . upon close examination
, threads of supportive findings may unravel , and when contrary evidence is properly considered , an otherwise impressive mass of findings may collapse . a large part of their response is a long catalog of supportive data  some of which i included in my review .
however , as i pointed out , careful examination reveals alternative explanations for some of their results .
they also largely ignore evidence consistent with net increases in synaptic strength after sleep , or findings that question their hypothesized relationship between synaptic potentiation and slow - wave electroencephalographic activity ( swa ) [ 11 , 12 ] .
these findings are consistent with my original discussion   and completely in opposition to predictions of shy .
when these are also considered the universality of shy , and its utility as an explanation for why we sleep , becomes questionable .
  in my original review , i considered biological processes other than sleep that might explain some findings ascribed to shy .
these included the cumulative effects of natural patterns in brain temperature ( and in mammals , glucocorticoid release ) across the 24-hour day or after sleep deprivation .
tononi and cirelli present a number of arguments against these ideas , but i have a better idea
for example , why not examine the effects of cooling or warming on drosophila synaptic proteins ( which are altered by changes in temperature as small as 8c ; not as they state 20c ) ?
tononi and cirelli argue strenuously that shy is a theory of function , yet they support their argument with cellular and molecular findings that have no demonstrable function . rather than elaborate upon already dense theoretical arguments about the functional importance of shy , why not demonstrate it empirically ? in science , no argument , no matter how beautifully crafted , trumps a good experiment .
  in his discussion of sleep theories 50 years ago , nathaniel kleitman reminded his readers of the cautionary tale of ptolemy of alexandria .
ptolemy was a revered scholar in the 2nd century ad who codified hundreds of years of prior greek astronomy and mathematics into what came to be known as the ptolemaic universe .
the ptolemaic universe held that the stars , planets and sun revolved around the earth , embedded in overlapping crystalline spheres .
this theory of the natural world was elegant , mathematical , and even highly predictive of astronomical events .
the lesson from ptolemy is that scientific theories are ultimately judged not only by their power to explain , but by the validity of their physical mechanisms .   
tononi and cirelli argue that for shy to be valid , it does not matter how synapses are weaker after a sleep period , just that they are .
but ptolemy reminds us that this is not enough ; scientific truth comes from asking hard questions about how things actually work .
i do not question their results , showing for example , changes in evoked responses or mrnas consistent with shy .
first , they have not identified how sleep actually alters synaptic strength in any species .
second , they have not experimentally excluded the role of other biological processes that coincide with sleep .
a final consideration is that if shy is a scientific hypothesis , then tononi and cirelli should propose an experimental outcome that would force a rejection of shy .
 in a recent article i reviewed an influential theory of sleep function , the  synaptic homeostasis hypothesis ( shy . )  according to shy , sleep renormalizes synapses that are potentiated during prior wakefulness . 
 i concluded that while shy is a seminal theory with important implications about sleep function and the brain , its underlying mechanisms are poorly defined . in an accompanying article , the authors of shy responded at length . 
 their reply is thoughtful and provocative , but unfortunately many of the points i raised were not accurately represented or addressed . in this brief commentary , i attempt to clarify some points of confusion . 
 i also explain why any theory of sleep function is incomplete without an understanding of the underlying cellular mechanisms . 