Table 2.

Impact on postnatal neurodevelopment of genetic manipulations of DA system

Perturbation	Species	Cellular-level changes	Brain region	Electrophysiological changes	Behavioral consequence	Reference (s)
Pitx3 −/−	Mouse	Lack of ontogenetic reduction in excitability (maturation) in dSPNs	Dorsal striatum	Elevated RMP and input resistance, more action potentials in response to injected current at P28	N/A	Lieberman et al., 2018
Pitx3 −/−	Mouse	Shorter dendritic trees ↓ spine density ↑ excitability	Striatum (dSPNs and iSPNs)	More action potentials evoked by depolarizing current and lower threshold	Impaired motor coordination (rotarod and beam transversal test)	Suarez et al., 2018
Pitx3 −/−	Mouse	↑ 5-HT innervation ↑ 5-HT2AR and SERT	Striatum	N/A	N/A	Li et al., 2013; Smits et al., 2008
Dysbindin mutant mice – increased surface D2R expression	Mouse	Spine deficiency	HPC	↓ mEPSC frequency	Impairment of spatial working memory	Jia et al., 2013
DAT +/−	Mouse	Decreased expression of Homer1a	PFC	N/A	Inattentive and impulsive phenotypes that can be rescued by low doses of amphetamine. Short-term memory deficits in adult females.	Mereu et al., 2017
DAT KD	Mouse	Long-lasting changes in cortico-striatal neurotransmission	Dorsal striatum	Altered amplitude and frequency of spontaneous glutamate receptor-mediated synaptic currents, shorter half-amplitude durations and faster decay times. No effect of AMPH or COC on spontaneous glutamate currents	↑ motivation, improved reversal learning	Wu et al., 2007; Milienne-Petiot et al., 2017
DAT −/−	Mouse	Highly localized loss of dendritic spines	Striatum MSNs	↓ amplitude of evoked DA release	Hyperactivity; impaired extinction of habitual memory; spatial learning and memory deficits; impaired behavioral inhibition	Berlanga et al., 2011; Hironaka et al., 2004; Jones et al., 1998; Gainetdinov et al., 1999;
DAT −/−	Rat	N/A	N/A	N/A	Hyperactivity working memory impairment, sensorimotor deficit; ↓ sensitivity to reward stimuli and compulsive stereotypy	Leo et al., 2018; Cinque et al., 2018
DAT Val559	Mouse	Anomalous DA efflux	Midbrain	Spontaneous and altered evoked D2R-mediated IPSCs	↑ motivation for reward, ↑ impulsivity; ↓ locomotor response to AMPH and MPH; Lack of cocaine-induced hyperlocomotion	Mazei-Robinson et al., 2008; Davis et al., 2018; Mergy et al., 2014; Stewart et al., 2019
DAT Val559	Mouse	↑ DAT surface expression	Striatum	Blunted AMPH- and 4-AP–Evoked DA Release, tonic presynaptic D2R stimulation	See above	Gowrishankar et al., 2018
DAT Met356	Mouse	Anomalous DA efflux and ↓ DA reuptake	Striatum	N/A	hyperlocomotion, altered social behavior, repetitive behavior	DiCarlo et al., 2019

Abbreviations: DA, dopamine; dSPNs, direct pathway spiny projection neurons; iSPNs, indirect pathway spiny projection neurons; RMP, resting membrane potential; N/A, not assessed; 5-HT, serotonin; 5-HT2AR, serotonin 2A receptor; SERT, serotonin transporter; HPC, hippocampus; mEPSC, miniature excitatory postsynaptic currents; PFC, prefrontal cortex; KD, knockdown; AMPH, amphetamine; COC, cocaine; MSNs, medium spiny neurons; D2R, dopamine D2 receptor; IPSCs, inhibitory postsynaptic currents; MPH, methylphenidate; DAT, dopamine transporter.