ABSTRACT
The main role of structures in ascending sensory systems is to extract raw features of sensory input and compartmentalize the information-bearing elements for use by the brain. Information-bearing elements can be apparent, as in the case of stimulus frequency or intensity (Ehret and Merzenich 1988; Tramo et al. 2002; Yu et al. 2010). The features of sound that drive neuronal fi ring at higher auditory centers, however, remain elusive. In their exciting article, Gill and colleagues (2008) show how “surprise” is a dimension of auditory experience that alters fi ring patterns of central auditory neurons. By elaborating the method for calculating and extracting spectro-temporal receptive fi elds (STRFs), the authors demonstrate that auditory neurons, mainly those from hierarchically higher-order areas, modulate their discharge rates in response to sound elements that deviate from expected values. This work is the fi rst to capture and separate encoding due to surprise from the ongoing encoding of spectral and temporal elements of acoustic cues (Theunissen et al. 2004). The coding of auditory information was studied in a highly social songbird species, the zebra fi nch (Taeniopygia guttata), which frequently engages in vocal exchange as part of its normal behaviour (for reviews, see Zeigler and Marler 2004). On the receiving (sensory) end of this exchange, the acoustic elements of the incoming birdsong, including notes and syllables, are encoded by auditory neurons (for reviews, see Mello et al. 2004; Gentner 2004). As with words in human speech, for a song to be recognizable over repeated use, the order of all of its individual sound elements must also be largely preserved across time. Consequently, songbirds naturally generate expectations not only for specifi c songs but also for the general structural rules, internal correlations or probability statistics that apply to song elements. To determine if surprise was predictive of altered neuronal activity, electrophysiological recordings were made in key structures of the ascending auditory pathway, including the songbird analogue of the mammalian inferior colliculus (nucleus MLd), the primary auditory forebrain area (Field L2) or an association auditory forebrain area (CLM) (Vates et al. 1996; Mello et al. 1998). One of the main goals of this work was to isolate the impact of surprise on auditory encoding for different cells (Gill et al. 2008). To this end, different forms of STRF were compared, including a STRF that was specifi cally developed to capture the impact of fi ring due to unmet expectations in stimulus structure (a surprise-STRF). In order to drive neuronal fi ring by surprise, Gill and colleagues generated song stimuli in which certain song elements were louder or softer than expected. Deviations were only introduced as changes in power for a particular element given a brief sample of “stimulus history”. This manipulation allowed for the measured and elegant application of “surprise” embedded on the song elements without having to interpret surprise in the context of the entire song. The authors show that surprise-STRF had far greater predictive strength relative to other STRF metrics and, therefore, was useful to parse out and quantify changes in fi ring given the probability of that change occurring based on prior experience. Surprise-STRFs were shown to have provided improvement in predictive power for select neurons at all three levels of the auditory pathway that were tested. Great gains in prediction were, however, frequently made by surprise-STRFs in the higher-order auditory area CLM, for two dominant cell types named by the authors as off-set and complex auditory neurons. Interestingly, in neurons that are surprise-responsive, Gill and colleagues found that the degree of altered fi ring was relatable, in linear terms, to the magnitude of change introduced. In addition, surprise coding was directionally sensitive; surprises to augmented stimulus power could be encoded at an entirely different sub-set of neurons than cells tuned to the surprise of a lower than expected stimulus power.
ABSTRACT
Glutamate, the main excitatory neurotransmitter in the vertebrate brain, acts both on ligand-gated ion channels as well as on metabotropic receptors (mGluRs), which engage an array of biochemical regulatory pathways via activation of G-proteins. mGluRs have been shown to exert central roles in the regulation of neuronal excitability by both pre- and post-synaptic mechanisms, and consequently have been implicated in a variety of central nervous system functions that include, but are not limited to, learning, pain perception and anxiety. There exists three groups of mGluRs (types I, II and III), accounting for a total of eight different mGluR types (mGluR1-8) (Hollmann and Heinemann 1994). Group I mGluRs, which encompass mGluR1 and mGluR5, engage Gq-dependent second messenger systems which, in turn, regulate post-synaptic activity and local protein synthesis. Abnormal signalling through group I mGluRs have been associated with a series of neurological disorders including Fragile X syndrome and schizophrenia (Dolen and Bear 2008; Krivoy et al. 2008). Importantly, group I mGluRs have been shown to regulate synaptic plasticity both in developing and adult organisms. Noteworthy, genetic or pharmacological manipulations directed at mGluR5-containing receptors signifi cantly impair learning and memory formation (Lu et al. 1997; Chiamulera et al. 2001). These roles for mGluR5 correlate with marked experience-dependent changes in synaptic strength, including long-term potentiation and depression (Eckert and Racine 2004). The impact of mGluR5 activity on synaptic function and plasticity suggested that activation of this receptor may constitute a central molecular component underlying the developmental establishment and/or experience-dependent refi nement of sensory maps found in primary sensory cortex of mammals. Such a role for mGluR5 was recently confi rmed in an elegant study by She and colleagues (2009) recently published in the European Journal of Neuroscience. These authors report that mice devoid of the mGluR5 receptor expression (mGluR5–/–) lack the normal arrangement of thalamocortical afferents and layer IV cell bodies associated with the rostral smaller whiskers of the facial vibrissal system, commonly referred to as the barrel cortex. Interestingly, the anatomical organisation of the thalamocortical afferents carrying information from the caudal and larger vibrissae was preserved in mGluR5–/– mice. These animals, however, lack the aggregation of the cortical layer IV cell bodies into clusters that would, in wild-type or heterozygous mice (mGluR5+/–), exclusively represent each vibrissa. In addition, it was found that mGluR5-null mice exhibit a striking mis-alignment of the dendritic fi elds of spiny stellate neurons, which contribute to the formation of the classic columnar neuronal arrangements typical of the barrel cortex. In particular, in intact mice, dendritic fi elds of layer IV neurons are normally oriented towards the barrel center, an organisation that putatively oversamples inputs from the dominant vibrissae to sharpen the perceptual experience of sensory drive from each whisker (Harris and Woolsey 1981). In mGluR5-defi cient mice, dendritic fi elds are more dispersed suggesting that pruning or mobility may be mal-adaptive in these animals, and may ultimately compromise the resolution at which sensory input can be processed. It was found that at post-natal weeks 2–3, mGluR5–/– mice failed to show the expected polarisation of dendritic fi elds towards the barrel center and that this abnormal pattern persists into adulthood. Interestingly, the anatomical patterning of axonal terminations from thalamocortical afferents was appropriate for barrel formation, and functional synaptic transmission for sensory-driven responses was spared. Malformation of the barrel cortex in mGluR5–/– therefore appears to result from abnormalities in intra-cortical properties and localised to post-synaptic neurons targeted by the thalamocortical afferents. Consistent with abnormalities in the formation of the barrel cortex in mGluR5–/– mice, these mutant animals show reduced latency to the surround whisker responses. This feature is shared with barrelless.