Biomedical Engineering Reference
In-Depth Information
M1—were optogenetically stimulated, the parkinsonian symptoms were relieved.
This study demonstrated that the excitatory afferent regulation of STN is at the heart
of the benefi cial outcome of deep-brain stimulation. Taken together, these results
promote our understanding of the functional connections within the basal ganglia
and may contribute to current therapeutic strategies to ameliorate parkinsonian
motor defi cits (Bernstein et al.
2008
).
8.2.4
Memory Formation and Reinforcement
The neural circuits based on reinforcement have been well characterized with opto-
genetic tools. Stimulation of dopaminergic neurons in the ventral tegmental area
co-released glutamate as well as dopamine into the nucleus accumbens, demonstrat-
ing that mesolimbic reward signaling involves glutamatergic transmission
(Tecuapetla et al.
2010
; Stuber et al.
2010
). Optical stimulation of
α
1-adrenergic
receptors in the nucleus accumbens, but not of
2-adrenergic receptors, led to a
robust increase in place preference during conditioning (Airan et al.
2009
). In addi-
tion, the relative contributions of distinct tonic versus phasic activity patterns in
participating brain structures, as well as the relative contributions of modulatory
systems with various neurotransmitters, are unknown (Stuber
2010
). By means of
optogenetics, selective phasic photostimulation of dopaminergic neurons in the ven-
tral tegmental area was shown to be suffi cient to establish association learning,
whereas tonic activation was not (Tsai et al.
2009
).
β
8.2.5
Anxiety and Aggression
Even a fairly deep part of the brain, the ventromedial hypothalamus (VMH), which
is thought to be closely related to instinctive behaviors, could be photostimulated
through an implanted optical fi ber. Optogenetic, but not electrical, stimulation of
neurons in the VMH ventrolateral subdivision (VMHvl) causes male mice to attack
both females and inanimate objects, as well as males (Lin et al.
2011
).
Another group, using of ChR2-assisted circuit mapping in amygdala slices and
cell-specifi c viral tracing, has reported that protein kinase C-d (PKC-d)1 neurons
inhibit output neurons in the medial central amygdala (CEm) and also make recipro-
cal inhibitory synapses with PKC-d2 neurons in the lateral subdivision of the central
amygdala (CEl). These results, together with behavioral data, defi ne an inhibitory
microcircuit in CEl that gates CEm output to control the level of conditioned freez-
ing (Haubensak et al.
2010
). In another study, specifi c optogenetic stimulation of
oxytocinergic axons in the amygdala was shown to reduce freezing responses in
fear-conditioned rats, illuminating the mechanisms by which oxytocin modifi es
emotional circuitry in a positive manner (Knobloch et al. 2012).
